BACKGROUND Blastic plasmacytoid dendritic cell tumor(BPDCN)is a rare and highly invasive lymphohematopoietic tumor that originates from plasmacytoid dendritic cells.BPDCN has an extremely poor prognosis.Skin lesions a...BACKGROUND Blastic plasmacytoid dendritic cell tumor(BPDCN)is a rare and highly invasive lymphohematopoietic tumor that originates from plasmacytoid dendritic cells.BPDCN has an extremely poor prognosis.Skin lesions are usually the first manifestation of BPDCN,although the tumor may also invade the bone marrow,lymph nodes,peripheral blood,and other parts of the body,leading to several other manifestations,requiring further differentiation through skin biopsy and immunohistochemistry.CASE SUMMARY In the present paper,the cases of 2 patients diagnosed with BPDCN are discussed.The immunohistochemistry analysis of these 2 patients revealed positivity for CD4,CD56,and CD123.Currently,no standard chemotherapy regimen is available for BPDCN.Therefore,intensive therapy for acute lymphoblastic leukemia was applied as the treatment method for these 2 cases.CONCLUSION Although allogeneic bone marrow transplantation could be further effective in prolonging the median survival the ultimate prognosis was unfavorable.Future treatment modalities tailored for elderly patients will help prolong survival.展开更多
We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin m...We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination.The article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this disease.These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.Furthermore,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission.The editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.展开更多
BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research...BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.展开更多
BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,ly...BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.展开更多
Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor pro...Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor prognosis with poor overall survival.BPDCN is derived from plasmacytoid dendritic cells(pDCs)and its pathogenesis is unclear.The tumor cells show aberrant expression of CD4,CD56,interleukin-3 receptor alpha chain(CD 123),blood dendritic cell antigen 2(BDCA 2/CD303),blood dendritic cell antigen 4(BDCA4)and transcription factor(E protein)E2-2(TCF4).The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma.Relapse with drug resistance generally occurs quickly.Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy.In this review,we summarize the differentiation of BPDCN from its cell origin,its connection with normal pDCs,clinical characteristics,genetic mutations and advances in treatment of BPDCN.This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.展开更多
The major difficulties of human papillomavirus(HPV) treatment are its persistence and recurrence. The HPV E7 oncoprotein-loaded dendritic cells have been evaluated as cellular vaccine in previous reports. Plasmacytoid...The major difficulties of human papillomavirus(HPV) treatment are its persistence and recurrence. The HPV E7 oncoprotein-loaded dendritic cells have been evaluated as cellular vaccine in previous reports. Plasmacytoid dendritic cells(pDCs) play an essential role of connecting the innate immune response and adaptive immune response in the immune system. But they function in HPV E7 loading is unclear. To investigate whether loading of the HPV type 6b, 11, and 16 E7 proteins affects the activity of pDCs, human peripheral blood-separated pDCs and mouse bone marrow-derived pDCs were pulsed with the HPV E7 proteins. The expression levels of CD40, CD80, CD86, and MHC II were significantly upregulated in pDCs upon HPV 6b/11 E7 protein pulse. The secretion and gene expression of type I IFN and IL-6 were both upregulated by HPV 6b/11 E7 proteins, more significant than HPV 16 E7 protein. The expression of essential factors of TLR signaling pathway and JNK/p38 MAP kinase signaling pathway were all increased in HPV 6b/11 E7 proteins pulsed pDCs. Our results suggest that HPV E7 proteins could promote the differentiation and maturation of pDCs and activate the TLR and MAPK pathway to induce host innate immune response. It might be conducive to explore novel immunotherapy targeting HPV infection with HPV E7 loaded pDC.展开更多
Objective： To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the...Objective： To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods： Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results： A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion： The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.展开更多
Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME...Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.展开更多
Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions Plasmacytoid dendritic cells （pDCs） have been found to participate in the progres...Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions Plasmacytoid dendritic cells （pDCs） have been found to participate in the progression of atherosclerosis mainly through interferon ct （IFN-ct） production. Whether cilostazol influences pDCs activation is still not clear. In this study, we aimed to investigate the effects of cilostazol on cell activation and antigen presentation ofpDCs in vitro in this study. Methods Peripheral blood mononuclear cells isolated by Ficoll cen- trifugation and pDCs sorted by flow cytometry were used in this study. After pretreated with cilostazol for 2 h, cells were stimulated with CpG-A, R848 or virus for 6 h or 20 h, or stimulated with CpG-B for 48 h and then co-cultured with naive T cell for five days. Cytokines in supernatant and intracellular cytokines were analyzed by ELISA or flow cytometry respectively. Results Our data indicated that cilostazol could inhibit IFN-α and tumor necrosis factor α （TNF-α） production from pDCs in a dose-dependent manner. In addition, the ability of priming na ve T cells of pDCs was also impaired by cilostazol. The inhibitory effect was not due to cell killing since the viability of pDCs did not change upon cilostazol treatment. Conclusion Cilostazol inhibits pDCs cell activation and antigen presentation in vitro, which may explain how cilostazol protects against atherosclerosis.展开更多
BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and highly aggressive hematopoietic malignancy.BPDCN is difficult to diagnose because of the overlap in morphologic and immunophenotypic features...BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and highly aggressive hematopoietic malignancy.BPDCN is difficult to diagnose because of the overlap in morphologic and immunophenotypic features with various cutaneous lymphatic hematopoietic tumors.CASE SUMMARY We report on three BPDCN cases,all characterized by skin nodules and examined by histology,immunohistochemical detection,in situ hybridization for Epstein-Barr virus,and follow-up.We also review the relevant literature.All patients were positive for CD56 and negative for Epstein-Barr encoded small RNA.Two patients had bone marrow involvement.Chemotherapy is the main treatment for BPDCN,but case 1 showed bone marrow suppression and case 2 developed recurrence after chemotherapy.Case 1 survived for 7 mo,case 2 for 17 mo,and case 3 for 9 mo.CONCLUSION An accurate pathological diagnosis is a precondition for treatment,and the diagnosis of BPDCN should be based on a combination of clinical symptoms,pathological characteristics,immunophenotype,and other auxiliary examinations.It is necessary to clarify the clinicopathological features and biological behavior of BPDCN to improve its understanding by both clinicians and pathologists.Case 2 survived significantly longer than the other two cases,suggesting that the treatment received by case 2 was more effective.展开更多
The mechanisms involved in resistance to HIV-1 infection, especially the role of innate immune response, have not been thoroughly explored in individuals who are repeatedly exposed to HIV-1, but do not get the infecti...The mechanisms involved in resistance to HIV-1 infection, especially the role of innate immune response, have not been thoroughly explored in individuals who are repeatedly exposed to HIV-1, but do not get the infection, termed as Exposed sero-negative or ESN. Frequency and activation state of natural killer (NK) cells and plasmacytoid dendritic cells (pDC) in ESNs from North India were compared with those in recently infected HIV positives (RHIV), chronically infected HIV positives (HIV+) and healthy controls (HC). The activation state of NK cells in terms of cytokine response (IFNγ & TNFα) was significantly higher in ESNs compared to the healthy controls, recently infected HIV+ and chronically infected HIV+. Although the number of circulating pDC in different study groups was not significantly different, yet these cells seem to have significantly higher activation state in terms of IFNα production (ex-vivo in response to CpG ODN) in ESNs when compared with other groups. Increased activation status of NK cells and pDC in Exposed but Seronegative individuals indicates their continuous stimulation with HIV antigens due to regular exposure with infected partners and which might be imparting resistance to viral infection in these individuals.展开更多
OBJECTIVE To study the mechanism of IFN on CML.METHODS Samples of 15 CML patients and 10 healthy controlswere studied. The flow cytometry was performed to identifycirculating pDCs. The concentration of IFN-α in serum...OBJECTIVE To study the mechanism of IFN on CML.METHODS Samples of 15 CML patients and 10 healthy controlswere studied. The flow cytometry was performed to identifycirculating pDCs. The concentration of IFN-α in serum and that inthe supernatant of peripheral blood mononuclear cells (PBMCs)cultured after stimulation with CpG ODN2216 were examinedboth in CML patients and in the healthy controlsRESULTS There was significant reduction in the numberof circulating pDCs, serum concentration of IFN-α and thecapacity of IFN-α producing PBMCs in CML patients comparedwith those in healthy control individuals (P < 0.001). After theactive treatment with IFN-α and hydroxyurea, the quantity andfunction of pDCs were increased in stabilized patients, especiallythe function of pDCs in 2 patients achieving major cytogeneticresponse (MCR). The proportion and function of pDCs and theserum levels of IFN were inversely correlated with both WBC andage of the patients with CML, and positively correlated with thestate of the illness.CONCLUSION CML patients had a reduced number anddysfunction of circulating pDCs. The active treatment with IFN inCML patients may be related to the restoration of pDCs.展开更多
BACKGROUND Plasmacytoid urothelial carcinoma(PUC)is a rare histologic variant of urothelial carcinoma.PUC is characterized by aggressiveness and poor prognosis.Since the first reported case of PUC in 1991,approximatel...BACKGROUND Plasmacytoid urothelial carcinoma(PUC)is a rare histologic variant of urothelial carcinoma.PUC is characterized by aggressiveness and poor prognosis.Since the first reported case of PUC in 1991,approximately 100 cases have been documented.In patients with PUC,colorectal metastasis is an uncommon presentation that is difficult to diagnose because it can mimic colitis on imaging examination,exhibiting colorectal wall thickening with a preserved vesicorectal fat plane.The pathogenesis of urologic malignancies that metastasize to the colon remains unclear.CASE SUMMARY A 65-year-old Taiwan resident,China man presented to our emergency department with a 3-month history of progressive abdominal fullness.A month before presentation,he had visited our hospital for gross hematuria with hydronephrosis and was subsequently hospitalized in our urology ward for transurethral resection of a bladder tumor.Postoperative histopathologic examination confirmed PUC.Regarding the illness at presentation,abdominal computed tomography revealed diffuse distension of the small and large intestines and long segmental thickening of the rectosigmoid colonic wall.Conservative management—empirical antibiotics,bowel rest,nasogastric tube decompression,and intravenous fluid support—was initiated with a presumptive diagnosis of colitis.Because of the patient’s inadequate response to conservative management,a diverting ileostomy was performed,which relieved the abdominal distension.Subsequent colonoscopic and histopathologic examinations with immunohistochemical staining confirmed colorectal metastasis through an atypical metastatic route.CONCLUSION Our case highlights diagnostic challenges posed by atypical imaging findings and unusual etiologies of gastrointestinal wall thickening with peripheral infiltration.展开更多
Type I and III interferons(IFNs)are essential for antiviral immunity and act through two different but complimentary pathways.First,IFNs activate intracellular antimicrobial programs by triggering the upregulation of ...Type I and III interferons(IFNs)are essential for antiviral immunity and act through two different but complimentary pathways.First,IFNs activate intracellular antimicrobial programs by triggering the upregulation of a broad repertoire of viral restriction factors.Second,IFNs activate innate and adaptive immunity.Dysregulation of IFN production can lead to severe immune system dysfunction.It is thus crucial to identify and characterize the cellular sources of IFNs,their effects,and their regulation to promote their beneficial effects and limit their detrimental effects,which can depend on the nature of the infected or diseased tissues,as we will discuss.Plasmacytoid dendritic cells(pDCs)can produce large amounts of all IFN subtypes during viral infection.pDCs are resistant to infection by many different viruses,thus inhibiting the immune evasion mechanisms of viruses that target IFN production or their downstream responses.Therefore,pDCs are considered essential for the control of viral infections and the establishment of protective immunity.A thorough bibliographical survey showed that,in most viral infections,despite being major IFN producers,pDCs are actually dispensable for host resistance,which is achieved by multiple IFN sources depending on the tissue.Moreover,primary innate and adaptive antiviral immune responses are only transiently affected in the absence of pDCs.More surprisingly,pDCs and their IFNs can be detrimental in some viral infections or autoimmune diseases.This makes the conservation of pDCs during vertebrate evolution an enigma and thus raises outstanding questions about their role not only in viral infections but also in other diseases and under physiological conditions.展开更多
Plasmacytoid dendritic cells (pDCs) represent a unique and crucial immune cell population capable of producing large amounts of type I interferons (IFNs) in response to viral infection.The function of pDCs as the prof...Plasmacytoid dendritic cells (pDCs) represent a unique and crucial immune cell population capable of producing large amounts of type I interferons (IFNs) in response to viral infection.The function of pDCs as the professional type I IFN-producing cells is linked to their selective expression of Toll-like receptor 7 (TLR7) and TLR9,which sense viral nucleic acids within the endosomal compartments.Type I IFNs produced by pDCs not only directly inhibit viral replication but also play an essential role in linking the innate and adaptive immune system.The aberrant activation of pDCs by self nucleic acids through TLR signaling and the ongoing production of type I IFNs do occur in some autoimmune diseases.Therefore,pDC may serve as an attractive target for therapeutic manipulations of the immune system to treat viral infectious diseases and autoimmune diseases.展开更多
Appropriate in vivo control of plasmacytoid dendritic cell （pDC） recruitment and activation is a fundamental requirement for defense against viral infection. During this process, a pivotal event that influences the ...Appropriate in vivo control of plasmacytoid dendritic cell （pDC） recruitment and activation is a fundamental requirement for defense against viral infection. During this process, a pivotal event that influences the outcome of viral infection is the production of high levels of type I interferon by pDCs. In particular, recent research findings showed that pDCs not only shape the nature of innate resistance, but are also responsible for the successful transition from innate to adaptive immunity for viral resistance. In addition, pDCs can differentiate into antigen presenting cells that may regulate tolerance to a given pathogen. Importantly, in a series of recent clinical studies, pDCs appeared to be defective in number and function in conditions of chronic viral diseases such as infected with HIV-1, HBV or HCV. pDC-associated clinical antiviral therapy is also emerging. This review describes research findings exatnining the functional and antiviral properties of in vivo pDC plasticity. Cellular ＆ Molecular Immunology. 2005;2（6）：411- 417.展开更多
Plasmacytoid dendritic cells(pDCs),also known as type I interferon(IFN)-producing cells,are specialized immune cells characterized by their extraordinary capabilities of mounting rapid and massive type I IFN response ...Plasmacytoid dendritic cells(pDCs),also known as type I interferon(IFN)-producing cells,are specialized immune cells characterized by their extraordinary capabilities of mounting rapid and massive type I IFN response to nu-cleic acids derived from virus,bacteria or dead cells.PDCs selectively express endosomal Toll-like receptor(TLR)7 and TLR9,which sense viral RNA and DNA re-spectively.Following type I IFN and cytokine responses,pDCs differentiate into antigen presenting cells and ac-quire the ability to regulate T cell-mediated adaptive immunity.The functions of pDCs have been implicated not only in antiviral innate immunity but also in immune tolerance,inflammation and tumor microenvironments.In this review,we will focus on TLR7/9 signaling and their regulation by pDC-specific receptors.展开更多
Acute kidney injury(AKI)is a common clinical complication associated with high mortality in patients.Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis.Plasmacytoid den...Acute kidney injury(AKI)is a common clinical complication associated with high mortality in patients.Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis.Plasmacytoid dendritic cells(pDCs)are a unique DC subset that specializes in type Ⅰ interferon(IFN)production.Here,we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α.Deletion of pDCs using DTR^(BDCA2) transgenic(Tg)mice suppressed cisplatin-induced AKI,accompanied by marked reductions in proinflammatory cytokine production,immune cell infiltration and apoptosis in the kidney.In contrast,adoptive transfer of pDCs during AKI exacerbated kidney damage.We further identified IFN-α as the key factor that mediated the functions of pDCs during AKI,as IFN-α neutralization significantly attenuated kidney injury.Furthermore,IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells(TECs)in vitro.In addition,our data demonstrated that apoptotic TECs induced the activation of pDCs,which was inhibited in the presence of an apoptosis inhibitor.Furthermore,similar deleterious effects of pDCs were observed in an ischemia reperfusion(IR)-induced AKI model.Clinically,increased expression of IFN-α in kidney biopsies was observed in kidney transplants with AKI.Taken together,the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.展开更多
基金Supported by The National Key Research and Development Programs of China,No.2022YFC2603801Maternal and Child Health Project of Jiangsu Province,No.F201717+1 种基金Doctor Project of Affiliated Hospital of Jiangsu University,No.jdfyrc2019003Clinical and Virology Study of 2019-ncov Infection in Patients with Moderate to Severe Psoriasis,No.Jdfyxgzx005.
文摘BACKGROUND Blastic plasmacytoid dendritic cell tumor(BPDCN)is a rare and highly invasive lymphohematopoietic tumor that originates from plasmacytoid dendritic cells.BPDCN has an extremely poor prognosis.Skin lesions are usually the first manifestation of BPDCN,although the tumor may also invade the bone marrow,lymph nodes,peripheral blood,and other parts of the body,leading to several other manifestations,requiring further differentiation through skin biopsy and immunohistochemistry.CASE SUMMARY In the present paper,the cases of 2 patients diagnosed with BPDCN are discussed.The immunohistochemistry analysis of these 2 patients revealed positivity for CD4,CD56,and CD123.Currently,no standard chemotherapy regimen is available for BPDCN.Therefore,intensive therapy for acute lymphoblastic leukemia was applied as the treatment method for these 2 cases.CONCLUSION Although allogeneic bone marrow transplantation could be further effective in prolonging the median survival the ultimate prognosis was unfavorable.Future treatment modalities tailored for elderly patients will help prolong survival.
基金Supported by The Chongqing Health Commission and Science and Technology Bureau,No.2023MSXM060.
文摘We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination.The article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this disease.These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.Furthermore,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission.The editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.
文摘BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.
文摘BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.
基金the National NaOiral Science Foundation of China(No.81460030,81770221).
文摘Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor prognosis with poor overall survival.BPDCN is derived from plasmacytoid dendritic cells(pDCs)and its pathogenesis is unclear.The tumor cells show aberrant expression of CD4,CD56,interleukin-3 receptor alpha chain(CD 123),blood dendritic cell antigen 2(BDCA 2/CD303),blood dendritic cell antigen 4(BDCA4)and transcription factor(E protein)E2-2(TCF4).The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma.Relapse with drug resistance generally occurs quickly.Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy.In this review,we summarize the differentiation of BPDCN from its cell origin,its connection with normal pDCs,clinical characteristics,genetic mutations and advances in treatment of BPDCN.This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.
基金supported by National Natural Science Foundation of China (Grant Nos. 81301375, 31600655 and 81472889)the National Health and Family Planning Commission Research Foundation of China (Grant No. 2015117502)
文摘The major difficulties of human papillomavirus(HPV) treatment are its persistence and recurrence. The HPV E7 oncoprotein-loaded dendritic cells have been evaluated as cellular vaccine in previous reports. Plasmacytoid dendritic cells(pDCs) play an essential role of connecting the innate immune response and adaptive immune response in the immune system. But they function in HPV E7 loading is unclear. To investigate whether loading of the HPV type 6b, 11, and 16 E7 proteins affects the activity of pDCs, human peripheral blood-separated pDCs and mouse bone marrow-derived pDCs were pulsed with the HPV E7 proteins. The expression levels of CD40, CD80, CD86, and MHC II were significantly upregulated in pDCs upon HPV 6b/11 E7 protein pulse. The secretion and gene expression of type I IFN and IL-6 were both upregulated by HPV 6b/11 E7 proteins, more significant than HPV 16 E7 protein. The expression of essential factors of TLR signaling pathway and JNK/p38 MAP kinase signaling pathway were all increased in HPV 6b/11 E7 proteins pulsed pDCs. Our results suggest that HPV E7 proteins could promote the differentiation and maturation of pDCs and activate the TLR and MAPK pathway to induce host innate immune response. It might be conducive to explore novel immunotherapy targeting HPV infection with HPV E7 loaded pDC.
文摘Objective： To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods： Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results： A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion： The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.
基金supported by grants from the China Postdoctoral Science Foundation(Grant No.2022M712880)the Program of the Major Research Plan of the National Natural Science Foundation of China(Grant No.91942314)the National Natural Science Foundation of China(Grant No.82001659).
文摘Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.
文摘Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions Plasmacytoid dendritic cells （pDCs） have been found to participate in the progression of atherosclerosis mainly through interferon ct （IFN-ct） production. Whether cilostazol influences pDCs activation is still not clear. In this study, we aimed to investigate the effects of cilostazol on cell activation and antigen presentation ofpDCs in vitro in this study. Methods Peripheral blood mononuclear cells isolated by Ficoll cen- trifugation and pDCs sorted by flow cytometry were used in this study. After pretreated with cilostazol for 2 h, cells were stimulated with CpG-A, R848 or virus for 6 h or 20 h, or stimulated with CpG-B for 48 h and then co-cultured with naive T cell for five days. Cytokines in supernatant and intracellular cytokines were analyzed by ELISA or flow cytometry respectively. Results Our data indicated that cilostazol could inhibit IFN-α and tumor necrosis factor α （TNF-α） production from pDCs in a dose-dependent manner. In addition, the ability of priming na ve T cells of pDCs was also impaired by cilostazol. The inhibitory effect was not due to cell killing since the viability of pDCs did not change upon cilostazol treatment. Conclusion Cilostazol inhibits pDCs cell activation and antigen presentation in vitro, which may explain how cilostazol protects against atherosclerosis.
文摘BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and highly aggressive hematopoietic malignancy.BPDCN is difficult to diagnose because of the overlap in morphologic and immunophenotypic features with various cutaneous lymphatic hematopoietic tumors.CASE SUMMARY We report on three BPDCN cases,all characterized by skin nodules and examined by histology,immunohistochemical detection,in situ hybridization for Epstein-Barr virus,and follow-up.We also review the relevant literature.All patients were positive for CD56 and negative for Epstein-Barr encoded small RNA.Two patients had bone marrow involvement.Chemotherapy is the main treatment for BPDCN,but case 1 showed bone marrow suppression and case 2 developed recurrence after chemotherapy.Case 1 survived for 7 mo,case 2 for 17 mo,and case 3 for 9 mo.CONCLUSION An accurate pathological diagnosis is a precondition for treatment,and the diagnosis of BPDCN should be based on a combination of clinical symptoms,pathological characteristics,immunophenotype,and other auxiliary examinations.It is necessary to clarify the clinicopathological features and biological behavior of BPDCN to improve its understanding by both clinicians and pathologists.Case 2 survived significantly longer than the other two cases,suggesting that the treatment received by case 2 was more effective.
文摘The mechanisms involved in resistance to HIV-1 infection, especially the role of innate immune response, have not been thoroughly explored in individuals who are repeatedly exposed to HIV-1, but do not get the infection, termed as Exposed sero-negative or ESN. Frequency and activation state of natural killer (NK) cells and plasmacytoid dendritic cells (pDC) in ESNs from North India were compared with those in recently infected HIV positives (RHIV), chronically infected HIV positives (HIV+) and healthy controls (HC). The activation state of NK cells in terms of cytokine response (IFNγ & TNFα) was significantly higher in ESNs compared to the healthy controls, recently infected HIV+ and chronically infected HIV+. Although the number of circulating pDC in different study groups was not significantly different, yet these cells seem to have significantly higher activation state in terms of IFNα production (ex-vivo in response to CpG ODN) in ESNs when compared with other groups. Increased activation status of NK cells and pDC in Exposed but Seronegative individuals indicates their continuous stimulation with HIV antigens due to regular exposure with infected partners and which might be imparting resistance to viral infection in these individuals.
基金supported by a grant from the Science and Technology Planning Project of Gansu Province,China(No.2005LZ0627).
文摘OBJECTIVE To study the mechanism of IFN on CML.METHODS Samples of 15 CML patients and 10 healthy controlswere studied. The flow cytometry was performed to identifycirculating pDCs. The concentration of IFN-α in serum and that inthe supernatant of peripheral blood mononuclear cells (PBMCs)cultured after stimulation with CpG ODN2216 were examinedboth in CML patients and in the healthy controlsRESULTS There was significant reduction in the numberof circulating pDCs, serum concentration of IFN-α and thecapacity of IFN-α producing PBMCs in CML patients comparedwith those in healthy control individuals (P < 0.001). After theactive treatment with IFN-α and hydroxyurea, the quantity andfunction of pDCs were increased in stabilized patients, especiallythe function of pDCs in 2 patients achieving major cytogeneticresponse (MCR). The proportion and function of pDCs and theserum levels of IFN were inversely correlated with both WBC andage of the patients with CML, and positively correlated with thestate of the illness.CONCLUSION CML patients had a reduced number anddysfunction of circulating pDCs. The active treatment with IFN inCML patients may be related to the restoration of pDCs.
文摘BACKGROUND Plasmacytoid urothelial carcinoma(PUC)is a rare histologic variant of urothelial carcinoma.PUC is characterized by aggressiveness and poor prognosis.Since the first reported case of PUC in 1991,approximately 100 cases have been documented.In patients with PUC,colorectal metastasis is an uncommon presentation that is difficult to diagnose because it can mimic colitis on imaging examination,exhibiting colorectal wall thickening with a preserved vesicorectal fat plane.The pathogenesis of urologic malignancies that metastasize to the colon remains unclear.CASE SUMMARY A 65-year-old Taiwan resident,China man presented to our emergency department with a 3-month history of progressive abdominal fullness.A month before presentation,he had visited our hospital for gross hematuria with hydronephrosis and was subsequently hospitalized in our urology ward for transurethral resection of a bladder tumor.Postoperative histopathologic examination confirmed PUC.Regarding the illness at presentation,abdominal computed tomography revealed diffuse distension of the small and large intestines and long segmental thickening of the rectosigmoid colonic wall.Conservative management—empirical antibiotics,bowel rest,nasogastric tube decompression,and intravenous fluid support—was initiated with a presumptive diagnosis of colitis.Because of the patient’s inadequate response to conservative management,a diverting ileostomy was performed,which relieved the abdominal distension.Subsequent colonoscopic and histopathologic examinations with immunohistochemical staining confirmed colorectal metastasis through an atypical metastatic route.CONCLUSION Our case highlights diagnostic challenges posed by atypical imaging findings and unusual etiologies of gastrointestinal wall thickening with peripheral infiltration.
基金supported by a fellowship from the French Ministry of Research and Higher Education.C.G.is supported by the French National Research Agency(no.ANR-21-CO15-0044-01,“DECITIP”,to E.T.).All the authors acknowledge institutional support from CNRS,INSERM,and Aix-Marseille Université.
文摘Type I and III interferons(IFNs)are essential for antiviral immunity and act through two different but complimentary pathways.First,IFNs activate intracellular antimicrobial programs by triggering the upregulation of a broad repertoire of viral restriction factors.Second,IFNs activate innate and adaptive immunity.Dysregulation of IFN production can lead to severe immune system dysfunction.It is thus crucial to identify and characterize the cellular sources of IFNs,their effects,and their regulation to promote their beneficial effects and limit their detrimental effects,which can depend on the nature of the infected or diseased tissues,as we will discuss.Plasmacytoid dendritic cells(pDCs)can produce large amounts of all IFN subtypes during viral infection.pDCs are resistant to infection by many different viruses,thus inhibiting the immune evasion mechanisms of viruses that target IFN production or their downstream responses.Therefore,pDCs are considered essential for the control of viral infections and the establishment of protective immunity.A thorough bibliographical survey showed that,in most viral infections,despite being major IFN producers,pDCs are actually dispensable for host resistance,which is achieved by multiple IFN sources depending on the tissue.Moreover,primary innate and adaptive antiviral immune responses are only transiently affected in the absence of pDCs.More surprisingly,pDCs and their IFNs can be detrimental in some viral infections or autoimmune diseases.This makes the conservation of pDCs during vertebrate evolution an enigma and thus raises outstanding questions about their role not only in viral infections but also in other diseases and under physiological conditions.
文摘Plasmacytoid dendritic cells (pDCs) represent a unique and crucial immune cell population capable of producing large amounts of type I interferons (IFNs) in response to viral infection.The function of pDCs as the professional type I IFN-producing cells is linked to their selective expression of Toll-like receptor 7 (TLR7) and TLR9,which sense viral nucleic acids within the endosomal compartments.Type I IFNs produced by pDCs not only directly inhibit viral replication but also play an essential role in linking the innate and adaptive immune system.The aberrant activation of pDCs by self nucleic acids through TLR signaling and the ongoing production of type I IFNs do occur in some autoimmune diseases.Therefore,pDC may serve as an attractive target for therapeutic manipulations of the immune system to treat viral infectious diseases and autoimmune diseases.
基金the National Outstanding Youth Foundation of China(No.30525042) National Key Basic Research Program of China(No.2001CB51003).
文摘Appropriate in vivo control of plasmacytoid dendritic cell （pDC） recruitment and activation is a fundamental requirement for defense against viral infection. During this process, a pivotal event that influences the outcome of viral infection is the production of high levels of type I interferon by pDCs. In particular, recent research findings showed that pDCs not only shape the nature of innate resistance, but are also responsible for the successful transition from innate to adaptive immunity for viral resistance. In addition, pDCs can differentiate into antigen presenting cells that may regulate tolerance to a given pathogen. Importantly, in a series of recent clinical studies, pDCs appeared to be defective in number and function in conditions of chronic viral diseases such as infected with HIV-1, HBV or HCV. pDC-associated clinical antiviral therapy is also emerging. This review describes research findings exatnining the functional and antiviral properties of in vivo pDC plasticity. Cellular ＆ Molecular Immunology. 2005;2（6）：411- 417.
文摘Plasmacytoid dendritic cells(pDCs),also known as type I interferon(IFN)-producing cells,are specialized immune cells characterized by their extraordinary capabilities of mounting rapid and massive type I IFN response to nu-cleic acids derived from virus,bacteria or dead cells.PDCs selectively express endosomal Toll-like receptor(TLR)7 and TLR9,which sense viral RNA and DNA re-spectively.Following type I IFN and cytokine responses,pDCs differentiate into antigen presenting cells and ac-quire the ability to regulate T cell-mediated adaptive immunity.The functions of pDCs have been implicated not only in antiviral innate immunity but also in immune tolerance,inflammation and tumor microenvironments.In this review,we will focus on TLR7/9 signaling and their regulation by pDC-specific receptors.
基金supported by grants from the National Natural Science Foundation of China(No:81870462 and 81470990 to F.Ding,No:91642112 to R.H.,and No:31600715 to Y.L.L.)The Science and Technology Commission of Shanghai Municipality(No:18140903300 to R.H.,No:17441904200 and 19441909300 to F.D.)+5 种基金Shanghai Ninth People’s Hospital Clinical Research Program(No:JYU007 to F.D.)Shanghai Ninth People's Hospital MDT Program(2017-1-019 to F.D.)Major Special Projects of the Ministry of Science and Technology(2018ZX10302207 to Y.L.L.)Development Project of Shanghai Peak Disciplines-Integrative Medicine(20180101 to Y.L.L.)Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine(BXJ201730 to B.D.)Fundamental Research Program Funding of Ninth People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine(JYZZ082B to B.D.).
文摘Acute kidney injury(AKI)is a common clinical complication associated with high mortality in patients.Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis.Plasmacytoid dendritic cells(pDCs)are a unique DC subset that specializes in type Ⅰ interferon(IFN)production.Here,we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α.Deletion of pDCs using DTR^(BDCA2) transgenic(Tg)mice suppressed cisplatin-induced AKI,accompanied by marked reductions in proinflammatory cytokine production,immune cell infiltration and apoptosis in the kidney.In contrast,adoptive transfer of pDCs during AKI exacerbated kidney damage.We further identified IFN-α as the key factor that mediated the functions of pDCs during AKI,as IFN-α neutralization significantly attenuated kidney injury.Furthermore,IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells(TECs)in vitro.In addition,our data demonstrated that apoptotic TECs induced the activation of pDCs,which was inhibited in the presence of an apoptosis inhibitor.Furthermore,similar deleterious effects of pDCs were observed in an ischemia reperfusion(IR)-induced AKI model.Clinically,increased expression of IFN-α in kidney biopsies was observed in kidney transplants with AKI.Taken together,the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.
