食管癌的发生、发展与许多因素有关,其中免疫系统发挥重要作用。CD47-SIRPα是PD-1/PD-L1,CTLA4之后的又一个免疫检查点,已经证明在多种血液系统肿瘤与实体瘤中高表达,通过产生抑制性信号阻止巨噬细胞吞噬癌细胞。本文针对其在食管癌中...食管癌的发生、发展与许多因素有关,其中免疫系统发挥重要作用。CD47-SIRPα是PD-1/PD-L1,CTLA4之后的又一个免疫检查点,已经证明在多种血液系统肿瘤与实体瘤中高表达,通过产生抑制性信号阻止巨噬细胞吞噬癌细胞。本文针对其在食管癌中的表达、与患者预后的关系、免疫治疗进行综述,通过本文的阐述,食管癌中的CD47-SIRPα同样是高表达,高CD47或高SIRPα都是导致食管癌患者预后不良的因素,抗CD47抗体与人源性食管癌细胞、人源性食管癌裸鼠模型有一定的结合活性。The occurrence and development of esophageal cancer are related to many factors, among which the immune system plays an important role. CD47-SIRPα is another immune checkpoint after PD-1/PD-L1 and CTLA4. It has been proved to be highly expressed in various hematological malignancies and solid tumors. It inhibits macrophage phagocytosis of cancer cells by generating inhibitory signals. This article reviews the expression of CD47-SIRPα in esophageal cancer, its relationship with the prognosis of patients, and immunotherapy. Through the elaboration of this article, CD47-SIRPα is also highly expressed in esophageal cancer. High CD47 or high SIRPα are both factors contributing to poor prognosis of patients with esophageal cancer, Anti-CD47 antibodies have certain binding activity with human esophageal cancer cells and human esophageal cancer nude mouse models.展开更多
Objective:To investigate the anti-tumor effects of an E1B55KD-deleted oncolytic adenovirus,H101,in combination with a humanized anti-PD-1(Programmed cell death protein 1)monoclonal antibody,Camrelizumab.Methods:Anti-t...Objective:To investigate the anti-tumor effects of an E1B55KD-deleted oncolytic adenovirus,H101,in combination with a humanized anti-PD-1(Programmed cell death protein 1)monoclonal antibody,Camrelizumab.Methods:Anti-tumor efficacy of intratumoral injection of H101 or/and intraperitoneal injection of Camrelizumab were evaluated in an immune system humanized NOD Prkdc^(scid) Il2rg^(-/-)mice subcutaneous(S.C.)tumor model,established with human glioblastoma of unknown origin cell line U87-MG,and human bladder cancer cell line T24 and YTS-1.The mechanism by which H101 induced anti-tumor immunity were also investigated.Results:Combining H101 with Camrelizumab demonstrated more potent anti-tumor effects than monotherapy in mouse S.C.tumor model.Increased tumor-infiltrating T cells were observed in the combined treatment group.H101 infection decreased the expression of CD47 in cancer cells,thereby promoting macrophages to phagocytose cancer cells.Following the H101-mediated activation of macrophages,increased levels of cytokines,including TNF,IL-12 and IFN-γwere observed.Moreover,when induced THP-1 cells were co-cultured with H101-treated cancer cells,expression of IFN-γwas increased in T cells.Elimination of IL-12 using an anti-IL-12 antibody abolished IFN-γproduction from T cells.In addition,infection with H101 increased PD-L1 expression in YTS-1 cells.These results suggested that H101 may act synergistically to enhance the therapeutic efficacy of PD-1 blockade in cancer via suppressing CD47 signaling,which may promote macrophages to phagocytose tumor cells and activate CD8^(+)T cells.Conclusion:The combination of H101 with PD-1 blockade exhibits potential as a novel strategy for the treatment of cancer.展开更多
Modern medicine faces the formidable challenge of cancer because of its ability to evade immune surveillance and cultivate resistance to conventional therapies. Cancer cells, when overexpressed with CD47, send a “don...Modern medicine faces the formidable challenge of cancer because of its ability to evade immune surveillance and cultivate resistance to conventional therapies. Cancer cells, when overexpressed with CD47, send a “don’t eat me” signal to macrophages, successfully shielding them from immune destruction. Similarly, tyrosine kinase inhibitors (TKIs) have revolutionized cancer treatment by targeting oncogenic pathways, but their effectiveness is often compromised by resistance and minimal residual disease. This review explores a novel combination of CD47-SIRP-blockade and TKIs, addressing the limitations of monotherapies in cancer treatment. Disrupting the CD47-SIRPα interaction stimulates macrophage-mediated phagocytosis and revives exhausted T cells, while TKIs simultaneously target tumor growth drivers. Confirmation from preclinical studies indicates that this combination is capable of enhancing anti-tumor immunity and remodeling tumor microenvironments for enhanced therapeutic outcomes. However, hematotoxicity and tumor heterogeneity present challenges in the path to clinical translation. This review presents current findings, identifies key research areas, and proposes future directions to enhance this combinatorial approach. In the midst of a new era in cancer treatment, immune modulation combined with targeted therapies promises to offer more effective, less toxic, and personalized treatment options. This combination approach has the potential to significantly improve cancer treatment strategies by overcoming current therapeutic limitations.展开更多
Cellular communication is required for the normal function and maintenance of homeostasis.The extracellular communications are mediated by cell surface receptors,which transmit signals for various cell functions.Cell ...Cellular communication is required for the normal function and maintenance of homeostasis.The extracellular communications are mediated by cell surface receptors,which transmit signals for various cell functions.Cell defense also relies on distinguishing between self and non-self.The integrins belong to the transmembrane receptors family and serve a crucial function in cell-extracellular adhesion and cell–cell signaling.The cell surface integrin-associated protein,or CD47,is an important integrin regulator and performs an array of functions.The CD47 interacts with the signal regulatory proteinα(SIRPα)and regulates adhesion,apoptosis,phagocytosis,proliferation,metabolism,activation,hematopoietic stem cell migration,and malignancies.The CD47 expression is increased in tumor cells to escape immune response.The anti-CD47 antibodies have shown promising therapeutic strategies in various clinical trials in the treatment of hematologic and solid tumors.In the current review,we discussed multifunctional roles,molecular mechanisms,and therapeutic strategies of tumors by utilizing CD47/SIRPαinteractions.展开更多
Gastrointestinal(GI)cancers are prevalent globally,with leading incidence and mortality rates among malignant tumors.Despite notable advancements in surgical resection,radiotherapy,and chemotherapy,the overall surviva...Gastrointestinal(GI)cancers are prevalent globally,with leading incidence and mortality rates among malignant tumors.Despite notable advancements in surgical resection,radiotherapy,and chemotherapy,the overall survival rates remain low.Hence,it is imperative to explore alternative approaches that enhance patient outcomes.Cluster of differentiation 47(CD47),serving as an early diagnostic marker,is predominantly overexpressed in GI cancers and associated with poor prognosis.Targeting the CD47-signal regulatory protein alpha(SIRPa)signaling pathway may provide a novel strategy for GI cancers treatment.This study summarizes current knowledge of the structure and function of CD47 and SIRPa,their roles in signaling pathways,the prognostic significance of CD47,therapeutic strategies targeting the CD47-SIRPα signaling pathway in GI cancer,and highlights key issues for future investigations.展开更多
目的探讨分化簇47(cluster of differentiation 47,CD47)与接受程序性死亡蛋白-1(programmed cell death protein 1,PD-1)/程序性死亡配体-1(programmed cell death ligand,PD-L1)抑制剂一线治疗的晚期非小细胞肺癌(Non-small cell lung...目的探讨分化簇47(cluster of differentiation 47,CD47)与接受程序性死亡蛋白-1(programmed cell death protein 1,PD-1)/程序性死亡配体-1(programmed cell death ligand,PD-L1)抑制剂一线治疗的晚期非小细胞肺癌(Non-small cell lung cancer,NSCLC)患者疗效及预后的相关性。方法收集2021年1月-2023年12月经湖南省邵阳市中心医院确诊为IIIB-IV期NSCLC且接受PD-1/PD-L1抑制剂一线治疗的116例患者的资料,获取患者的CD47蛋白表达情况并分析其与免疫治疗后疗效和预后的相关性。结果CD47阴性表达组患者的疾病控制率(disease control rate,DCR)高于阳性表达组(P=0.045)。在单因素生存分析中,CD47蛋白阴性表达患者的PFS优于CD47阳性表达组(P=0.002)。结论CD47蛋白阴性表达与晚期NSCLC患者接受免疫治疗后的疗效更好有关。展开更多
文摘食管癌的发生、发展与许多因素有关,其中免疫系统发挥重要作用。CD47-SIRPα是PD-1/PD-L1,CTLA4之后的又一个免疫检查点,已经证明在多种血液系统肿瘤与实体瘤中高表达,通过产生抑制性信号阻止巨噬细胞吞噬癌细胞。本文针对其在食管癌中的表达、与患者预后的关系、免疫治疗进行综述,通过本文的阐述,食管癌中的CD47-SIRPα同样是高表达,高CD47或高SIRPα都是导致食管癌患者预后不良的因素,抗CD47抗体与人源性食管癌细胞、人源性食管癌裸鼠模型有一定的结合活性。The occurrence and development of esophageal cancer are related to many factors, among which the immune system plays an important role. CD47-SIRPα is another immune checkpoint after PD-1/PD-L1 and CTLA4. It has been proved to be highly expressed in various hematological malignancies and solid tumors. It inhibits macrophage phagocytosis of cancer cells by generating inhibitory signals. This article reviews the expression of CD47-SIRPα in esophageal cancer, its relationship with the prognosis of patients, and immunotherapy. Through the elaboration of this article, CD47-SIRPα is also highly expressed in esophageal cancer. High CD47 or high SIRPα are both factors contributing to poor prognosis of patients with esophageal cancer, Anti-CD47 antibodies have certain binding activity with human esophageal cancer cells and human esophageal cancer nude mouse models.
基金supported by Techpool Bio-Pharma Co.,Ltd.(grant no.AKR-S005).
文摘Objective:To investigate the anti-tumor effects of an E1B55KD-deleted oncolytic adenovirus,H101,in combination with a humanized anti-PD-1(Programmed cell death protein 1)monoclonal antibody,Camrelizumab.Methods:Anti-tumor efficacy of intratumoral injection of H101 or/and intraperitoneal injection of Camrelizumab were evaluated in an immune system humanized NOD Prkdc^(scid) Il2rg^(-/-)mice subcutaneous(S.C.)tumor model,established with human glioblastoma of unknown origin cell line U87-MG,and human bladder cancer cell line T24 and YTS-1.The mechanism by which H101 induced anti-tumor immunity were also investigated.Results:Combining H101 with Camrelizumab demonstrated more potent anti-tumor effects than monotherapy in mouse S.C.tumor model.Increased tumor-infiltrating T cells were observed in the combined treatment group.H101 infection decreased the expression of CD47 in cancer cells,thereby promoting macrophages to phagocytose cancer cells.Following the H101-mediated activation of macrophages,increased levels of cytokines,including TNF,IL-12 and IFN-γwere observed.Moreover,when induced THP-1 cells were co-cultured with H101-treated cancer cells,expression of IFN-γwas increased in T cells.Elimination of IL-12 using an anti-IL-12 antibody abolished IFN-γproduction from T cells.In addition,infection with H101 increased PD-L1 expression in YTS-1 cells.These results suggested that H101 may act synergistically to enhance the therapeutic efficacy of PD-1 blockade in cancer via suppressing CD47 signaling,which may promote macrophages to phagocytose tumor cells and activate CD8^(+)T cells.Conclusion:The combination of H101 with PD-1 blockade exhibits potential as a novel strategy for the treatment of cancer.
文摘Modern medicine faces the formidable challenge of cancer because of its ability to evade immune surveillance and cultivate resistance to conventional therapies. Cancer cells, when overexpressed with CD47, send a “don’t eat me” signal to macrophages, successfully shielding them from immune destruction. Similarly, tyrosine kinase inhibitors (TKIs) have revolutionized cancer treatment by targeting oncogenic pathways, but their effectiveness is often compromised by resistance and minimal residual disease. This review explores a novel combination of CD47-SIRP-blockade and TKIs, addressing the limitations of monotherapies in cancer treatment. Disrupting the CD47-SIRPα interaction stimulates macrophage-mediated phagocytosis and revives exhausted T cells, while TKIs simultaneously target tumor growth drivers. Confirmation from preclinical studies indicates that this combination is capable of enhancing anti-tumor immunity and remodeling tumor microenvironments for enhanced therapeutic outcomes. However, hematotoxicity and tumor heterogeneity present challenges in the path to clinical translation. This review presents current findings, identifies key research areas, and proposes future directions to enhance this combinatorial approach. In the midst of a new era in cancer treatment, immune modulation combined with targeted therapies promises to offer more effective, less toxic, and personalized treatment options. This combination approach has the potential to significantly improve cancer treatment strategies by overcoming current therapeutic limitations.
基金Supported by Indian Council for Medical Research,No.56/2/Hae/BMSUniversity Grant Commission Start-Up Grant,No.30-496/2019.
文摘Cellular communication is required for the normal function and maintenance of homeostasis.The extracellular communications are mediated by cell surface receptors,which transmit signals for various cell functions.Cell defense also relies on distinguishing between self and non-self.The integrins belong to the transmembrane receptors family and serve a crucial function in cell-extracellular adhesion and cell–cell signaling.The cell surface integrin-associated protein,or CD47,is an important integrin regulator and performs an array of functions.The CD47 interacts with the signal regulatory proteinα(SIRPα)and regulates adhesion,apoptosis,phagocytosis,proliferation,metabolism,activation,hematopoietic stem cell migration,and malignancies.The CD47 expression is increased in tumor cells to escape immune response.The anti-CD47 antibodies have shown promising therapeutic strategies in various clinical trials in the treatment of hematologic and solid tumors.In the current review,we discussed multifunctional roles,molecular mechanisms,and therapeutic strategies of tumors by utilizing CD47/SIRPαinteractions.
基金supported by the Fundamental Research Funds for the Central Universities,China(Grant Nos.:2023CDJXY-009 and 2023CDJYGRH-YB07)the National Natural Science Foundation of China(Grant No.:82172888)the Natural Science Foundation Project of Chongqing Science and Technology Commission(Grant No.:cstc2020jcyj-msxmX0154).
文摘Gastrointestinal(GI)cancers are prevalent globally,with leading incidence and mortality rates among malignant tumors.Despite notable advancements in surgical resection,radiotherapy,and chemotherapy,the overall survival rates remain low.Hence,it is imperative to explore alternative approaches that enhance patient outcomes.Cluster of differentiation 47(CD47),serving as an early diagnostic marker,is predominantly overexpressed in GI cancers and associated with poor prognosis.Targeting the CD47-signal regulatory protein alpha(SIRPa)signaling pathway may provide a novel strategy for GI cancers treatment.This study summarizes current knowledge of the structure and function of CD47 and SIRPa,their roles in signaling pathways,the prognostic significance of CD47,therapeutic strategies targeting the CD47-SIRPα signaling pathway in GI cancer,and highlights key issues for future investigations.
文摘目的探讨分化簇47(cluster of differentiation 47,CD47)与接受程序性死亡蛋白-1(programmed cell death protein 1,PD-1)/程序性死亡配体-1(programmed cell death ligand,PD-L1)抑制剂一线治疗的晚期非小细胞肺癌(Non-small cell lung cancer,NSCLC)患者疗效及预后的相关性。方法收集2021年1月-2023年12月经湖南省邵阳市中心医院确诊为IIIB-IV期NSCLC且接受PD-1/PD-L1抑制剂一线治疗的116例患者的资料,获取患者的CD47蛋白表达情况并分析其与免疫治疗后疗效和预后的相关性。结果CD47阴性表达组患者的疾病控制率(disease control rate,DCR)高于阳性表达组(P=0.045)。在单因素生存分析中,CD47蛋白阴性表达患者的PFS优于CD47阳性表达组(P=0.002)。结论CD47蛋白阴性表达与晚期NSCLC患者接受免疫治疗后的疗效更好有关。
