Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their...Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their type, density and location are summarized in the Immune Score that has been shown to improve prognostic prediction of CRC patients. The non-classical MHC class I human leukocyte antigen-G (HLA-G), is a crucial tumor-driven immune escape molecule involved in immune tolerance. HLA-G and soluble counterparts are able to exert inhibitory functions by direct interactions with inhibitory receptors present on both innate cells such as natural killer cells, and adaptive immune cells as cytotoxic T and B lymphocytes. HLA-G may play a prominent role in CRC strategies to avoid host immunosurveillance. This review highlights the current knowledge on HLA-G contribution in CRC, in related inflammatory diseases and in other type of cancers and disorders. HLA-G genetic setting (specific haplotypes, genotypes and alleles frequencies) and association with circulating/soluble profiles was highlighted. HLA G prognostic and predictive value in CRC was investigated in order to define a novel prognostic immune biomarker in CRC.展开更多
Introduction: Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib antigen characterized by a limited polymorphism. The expression of HLA-G at immune privileged sites an...Introduction: Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib antigen characterized by a limited polymorphism. The expression of HLA-G at immune privileged sites and its ability to inhibit the effectors functions of immune cells has set HLA-G as a molecule of immune tolerance. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. Methods: Soluble HLA-G (sHLA-G) levels were measured using a BioVendor sHLA-G ELISA kit following the manufacturer’s protocol. The study participants include women undergoing spontaneous abortion, non-pregnant women, males and an archive sample of women who had normal vaginal deliveries without any complications and any history of malaria infection from gestation to delivery. Results: Soluble HLA-G levels were higher among women undergoing spontaneous abortion as compared to women who had normal vaginal delivery and non-pregnant women. Soluble HLA-G levels were also higher in second trimester as compared to first trimester in both women who had spontaneous abortions and women who had normal delivery. Conclusion: Although sHLA-G levels were higher among women undergoing spontaneous abortion as compared to non-pregnant women and women who had normal delivery, this may be playing a role in the maintenance of maternal immune tolerance to fetal antigen, since plasma sHLA-G levels increased with increasing trimester in both women who had normal delivery and women undergoing spontaneous abortion.展开更多
多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen...多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen receptor,CAR)T细胞疗法的快速发展,极大程度的改变了复发/难治性(relapsed/refractory,R/R)MM患者的治疗现状。FDA目前已批准了2款靶向B细胞成熟抗原(B cell maturation antigen,BCMA)的CAR-T细胞产品,使其用于既往接受过4线及以上治疗的R/R MM患者。随着临床研究的不断深入,靶向GPRC5D(G protein-coupled receptor C class Group 5 member D,G蛋白偶联受体C类第5组成员D)的CAR-T细胞治疗也显示出其独特的优势。除了应用于难治复发的患者,多项临床试验支持CAR-T在MM中治疗线数的前移。本文就CAR-T细胞治疗在MM中开展的关键性临床研究展开综述,旨在为临床应用提供参考。展开更多
Since discovery and cloning of the non-classical human leukocyte antigen （HLA） class Ⅰ antigen HLA-G by Geraghty et al in 1987, a large number of studies have been carried out. HLA-G has a low polymorphism, limited...Since discovery and cloning of the non-classical human leukocyte antigen （HLA） class Ⅰ antigen HLA-G by Geraghty et al in 1987, a large number of studies have been carried out. HLA-G has a low polymorphism, limited distribution to normal tissues and seven isoforms resulting from its primary mRNA alternative splicing. HLA-G expression was first found on the extravillous cytotrophoblasts, at the fetal-maternal interface during normal pregnancy, which lacks the expression of HLA-A, -B and HLA Ⅱ antigens. Initial studies on HLA-G mainly addressed its function in fetal-maternal immunotolerance. Two decades later, HLA-G is now considered to be a very important immune molecule which plays a vital immune inhibitory role in the context of reproduction, oncology, transplantation, infection and also in autoimmune disease. A number of Chinese research teams are interested in, and have contributed to, the publication of more than 80 peer-reviewed articles and reviews on HLA-G over the past ten years. We summarize the key points in this field that were presented and discussed by them.展开更多
BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicate...BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.展开更多
目的探究宫颈癌及癌前病变患者高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)感染现状及与血清人白细胞抗原-G(human leukocyte antigen-G,HLA-G)、高迁移率族蛋白A1(high mobility group protein A1,HMGA1)及转化生长因...目的探究宫颈癌及癌前病变患者高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)感染现状及与血清人白细胞抗原-G(human leukocyte antigen-G,HLA-G)、高迁移率族蛋白A1(high mobility group protein A1,HMGA1)及转化生长因子-β1(transforming growth factor-β1,TGF-β1)表达水平的相关性。方法选取2023年3月至2024年3月于重庆市开州区中医院接受治疗的148例宫颈癌患者,将其设为宫颈癌组,另选取同时期于医院接受治疗的92例宫颈上皮内瘤变(cervical intraepithelial neoplasias,CIN)患者,以及行健康体检的80例正常女性,分别将其设为癌前病变组和对照组。观察两组患者HR-HPV感染情况,以及三组受试者血清HLA-G、HMGA1、TGF-β1水平,同时分析血清HLA-G、HMGA1、TGF-β1水平与宫颈癌患者HR-HPV感染的相关性。结果癌前病变组中CINⅢ级HR-HPV感染率较CINⅠ级更高(χ^(2)=11.642,P=0.001),宫颈癌组子宫内膜癌的国际妇产科联盟(international federation of gynecology and obstetrics,FIGO)ⅠB期和FIGOⅡA期HR-HPV感染率均高于CINⅠ级、CINⅡ级和CINⅢ级(Z=22.045,Z=51.391,均P<0.001);宫颈癌组HR-HPV感染患者血清HLA-G、HMGA1、TGF-β1水平较非HR-HPV感染患者明显增高,癌前病变组HR-HPV感染患者血清HLA-G、HMGA1、TGF-β1水平高于非HR-HPV感染患者,差异均具有统计学意义(P<0.05)。宫颈癌组患者血清HLA-G、HMGA1、TGF-β1水平显著高于癌前病变组与对照组,癌前病变组患者血清HLA-G、HMGA1、TGF-β1水平高于对照组(P<0.05);通过Pearson相关系数分析得出,血清HLA-G、HMGA1、TGF-β1水平与宫颈癌患者HR-HPV感染均呈正相关(r=0.385,P<0.001;r=0.376,P<0.001;r=0.431,P<0.001)。结论宫颈癌与癌前病变患者HR-HPV感染率随病情进展升高,血清HLA-G、HMGA1、TGF-β1水平显著上调,且与HR-HPV感染密切相关,为宫颈癌的早期诊断等提供了新的生物标志物。展开更多
基金Supported by Associazione Italiana per la Ricerca sul Cancro(AIRC),Special Program Molecular Clinical Oncology,5X1000,No.12214(G.T.)European Research Council,Programme‘‘Ide-as’’,Proposal No.269051(G.T.,F.R.)
文摘Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their type, density and location are summarized in the Immune Score that has been shown to improve prognostic prediction of CRC patients. The non-classical MHC class I human leukocyte antigen-G (HLA-G), is a crucial tumor-driven immune escape molecule involved in immune tolerance. HLA-G and soluble counterparts are able to exert inhibitory functions by direct interactions with inhibitory receptors present on both innate cells such as natural killer cells, and adaptive immune cells as cytotoxic T and B lymphocytes. HLA-G may play a prominent role in CRC strategies to avoid host immunosurveillance. This review highlights the current knowledge on HLA-G contribution in CRC, in related inflammatory diseases and in other type of cancers and disorders. HLA-G genetic setting (specific haplotypes, genotypes and alleles frequencies) and association with circulating/soluble profiles was highlighted. HLA G prognostic and predictive value in CRC was investigated in order to define a novel prognostic immune biomarker in CRC.
文摘Introduction: Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib antigen characterized by a limited polymorphism. The expression of HLA-G at immune privileged sites and its ability to inhibit the effectors functions of immune cells has set HLA-G as a molecule of immune tolerance. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. Methods: Soluble HLA-G (sHLA-G) levels were measured using a BioVendor sHLA-G ELISA kit following the manufacturer’s protocol. The study participants include women undergoing spontaneous abortion, non-pregnant women, males and an archive sample of women who had normal vaginal deliveries without any complications and any history of malaria infection from gestation to delivery. Results: Soluble HLA-G levels were higher among women undergoing spontaneous abortion as compared to women who had normal vaginal delivery and non-pregnant women. Soluble HLA-G levels were also higher in second trimester as compared to first trimester in both women who had spontaneous abortions and women who had normal delivery. Conclusion: Although sHLA-G levels were higher among women undergoing spontaneous abortion as compared to non-pregnant women and women who had normal delivery, this may be playing a role in the maintenance of maternal immune tolerance to fetal antigen, since plasma sHLA-G levels increased with increasing trimester in both women who had normal delivery and women undergoing spontaneous abortion.
文摘多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen receptor,CAR)T细胞疗法的快速发展,极大程度的改变了复发/难治性(relapsed/refractory,R/R)MM患者的治疗现状。FDA目前已批准了2款靶向B细胞成熟抗原(B cell maturation antigen,BCMA)的CAR-T细胞产品,使其用于既往接受过4线及以上治疗的R/R MM患者。随着临床研究的不断深入,靶向GPRC5D(G protein-coupled receptor C class Group 5 member D,G蛋白偶联受体C类第5组成员D)的CAR-T细胞治疗也显示出其独特的优势。除了应用于难治复发的患者,多项临床试验支持CAR-T在MM中治疗线数的前移。本文就CAR-T细胞治疗在MM中开展的关键性临床研究展开综述,旨在为临床应用提供参考。
基金This work was supported by grants from the Natural Science Foundation of Zhejiang Province(No. Y205531 and No. Y205575)from the Ministry of Personnel.
文摘Since discovery and cloning of the non-classical human leukocyte antigen （HLA） class Ⅰ antigen HLA-G by Geraghty et al in 1987, a large number of studies have been carried out. HLA-G has a low polymorphism, limited distribution to normal tissues and seven isoforms resulting from its primary mRNA alternative splicing. HLA-G expression was first found on the extravillous cytotrophoblasts, at the fetal-maternal interface during normal pregnancy, which lacks the expression of HLA-A, -B and HLA Ⅱ antigens. Initial studies on HLA-G mainly addressed its function in fetal-maternal immunotolerance. Two decades later, HLA-G is now considered to be a very important immune molecule which plays a vital immune inhibitory role in the context of reproduction, oncology, transplantation, infection and also in autoimmune disease. A number of Chinese research teams are interested in, and have contributed to, the publication of more than 80 peer-reviewed articles and reviews on HLA-G over the past ten years. We summarize the key points in this field that were presented and discussed by them.
基金Supported by Hebei Province Medical Science Research Project Plan,No.20230755.
文摘BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.
文摘目的探究宫颈癌及癌前病变患者高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)感染现状及与血清人白细胞抗原-G(human leukocyte antigen-G,HLA-G)、高迁移率族蛋白A1(high mobility group protein A1,HMGA1)及转化生长因子-β1(transforming growth factor-β1,TGF-β1)表达水平的相关性。方法选取2023年3月至2024年3月于重庆市开州区中医院接受治疗的148例宫颈癌患者,将其设为宫颈癌组,另选取同时期于医院接受治疗的92例宫颈上皮内瘤变(cervical intraepithelial neoplasias,CIN)患者,以及行健康体检的80例正常女性,分别将其设为癌前病变组和对照组。观察两组患者HR-HPV感染情况,以及三组受试者血清HLA-G、HMGA1、TGF-β1水平,同时分析血清HLA-G、HMGA1、TGF-β1水平与宫颈癌患者HR-HPV感染的相关性。结果癌前病变组中CINⅢ级HR-HPV感染率较CINⅠ级更高(χ^(2)=11.642,P=0.001),宫颈癌组子宫内膜癌的国际妇产科联盟(international federation of gynecology and obstetrics,FIGO)ⅠB期和FIGOⅡA期HR-HPV感染率均高于CINⅠ级、CINⅡ级和CINⅢ级(Z=22.045,Z=51.391,均P<0.001);宫颈癌组HR-HPV感染患者血清HLA-G、HMGA1、TGF-β1水平较非HR-HPV感染患者明显增高,癌前病变组HR-HPV感染患者血清HLA-G、HMGA1、TGF-β1水平高于非HR-HPV感染患者,差异均具有统计学意义(P<0.05)。宫颈癌组患者血清HLA-G、HMGA1、TGF-β1水平显著高于癌前病变组与对照组,癌前病变组患者血清HLA-G、HMGA1、TGF-β1水平高于对照组(P<0.05);通过Pearson相关系数分析得出,血清HLA-G、HMGA1、TGF-β1水平与宫颈癌患者HR-HPV感染均呈正相关(r=0.385,P<0.001;r=0.376,P<0.001;r=0.431,P<0.001)。结论宫颈癌与癌前病变患者HR-HPV感染率随病情进展升高,血清HLA-G、HMGA1、TGF-β1水平显著上调,且与HR-HPV感染密切相关,为宫颈癌的早期诊断等提供了新的生物标志物。
