Background： Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma （NPC） patients. In this study, we evaluated the T cell response to melanoma-associated ...Background： Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma （NPC） patients. In this study, we evaluated the T cell response to melanoma-associated antigen （MAGE）-A1, MAGE-A3, or synovial sarcoma X-2 （SSX-2） in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen （HLA）-A types were analyzed to provide evidence of designing novel therapy. Methods： Sixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman＇s rank correlation was used to analyze the relationship of T cell responses. Results： HLA-A＊02：01, A＊02：07, and A＊24：02 were the three most frequent alleles （18.9%, 12.3%, and 11.5%, respectively） among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/106 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A＊02：01 and A＊24：02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders. Conclusion： MAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.展开更多
Background:Evading immune surveillance is necessary for tumor metastasis.Thus,there is an urgent need to better understand the interaction between metastasis and mechanisms of tumor immune evasion.In this study,we aim...Background:Evading immune surveillance is necessary for tumor metastasis.Thus,there is an urgent need to better understand the interaction between metastasis and mechanisms of tumor immune evasion.In this study,we aimed to clarify a novel mechanism that link tumor metastasis and immunosuppression in the development of esophageal squamous cell carcinoma(ESCC).Methods:The expression of melanoma-associated antigen C3(MAGE-C3)was detected using immunohistochemistry.Transwell assays were used to evaluate the migration and invasion ability of esophageal squamous cell carcinoma(ESCC)cells.Metastasis assays in mice were used to evaluate metastatic ability in vivo.Lymphocyte-mediated cytotoxicity assays were performed to visualize the immune suppression function on tumor cells.RNA sequencing was performed to identify differentially expressed genes between MAGE-C3 overexpressing ESCC cells and control cells.Gene ontology(GO)enrichment analyses was performed to identify the most altered pathways influenced by MAGE-C3.The activation of the interferon-γ(IFN-γ)pathway was analyzed using Western blotting,GAS luciferase reporter assays,immunofluorescence,and flow cytometry.The role of MAGE-C3 in the IFN-γpathway was determined by Western blotting and immunoprecipitation.Furthermore,immunohistochemistry and flow cytometry analysis monitored the changes of infiltrated T cell populations in murine lung metastases.Results:MAGE-C3 was overexpressed in ESCC tissues.High expression of MAGE-C3 had a significant association with the risk of lymphatic metastasis and poor survival in patients with ESCC.Functional experiments revealed that MAGE-C3 promoted tumor metastasis by activating the epithelial-mesenchymal transition(EMT).MAGE-C3 repressed antitumor immunity and regulated cytokine secretion of T cells,implying an immunosuppressive function.Mechanistically,MAGE-C3 facilitated IFN-γsignaling and upregulated programmed cell death ligand 1(PDŋL1)by binding with IFN-γreceptor 1(IFNGR1)and strengthening the interaction between IFNGR1展开更多
目的检测人脑膜瘤组织中黑色素瘤相关抗原MAGE-D4 m RNA的表达并分析其临床意义。方法采用逆转录-聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)方法,检测36例脑膜瘤组织和8例正常人脑组织中MAGE-D4 m RNA的表...目的检测人脑膜瘤组织中黑色素瘤相关抗原MAGE-D4 m RNA的表达并分析其临床意义。方法采用逆转录-聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)方法,检测36例脑膜瘤组织和8例正常人脑组织中MAGE-D4 m RNA的表达,分析MAGE-D4 m RNA的表达与脑膜瘤患者临床病理特征的关系。结果 MAGE-D4 m RNA在脑膜瘤组织中的阳性表达率为58.33%(21/36),明显高于正常人脑组织中的阳性表达率12.50%(1/8)(P<0.05);脑膜瘤组织中MAGE-D4 m RNA的表达与性别、年龄、肿瘤大小和病理类型等临床病理特征无关(P>0.05)。结论在脑膜瘤组织中MAGE-D4的表达率较高,提示MAGE-D4可能成为脑膜瘤免疫治疗的靶抗原。展开更多
文摘Background： Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma （NPC） patients. In this study, we evaluated the T cell response to melanoma-associated antigen （MAGE）-A1, MAGE-A3, or synovial sarcoma X-2 （SSX-2） in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen （HLA）-A types were analyzed to provide evidence of designing novel therapy. Methods： Sixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman＇s rank correlation was used to analyze the relationship of T cell responses. Results： HLA-A＊02：01, A＊02：07, and A＊24：02 were the three most frequent alleles （18.9%, 12.3%, and 11.5%, respectively） among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/106 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A＊02：01 and A＊24：02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders. Conclusion： MAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.
基金This study was supported by grants from the National Natural Science Foundation of China(81988101,81830086,82003007 and 81802780)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-081)+3 种基金Guangdong Basic and Applied Basic Research Foundation(2019B030302012)the Funding by Major Program of Shenzhen Bay Laboratory(S201101004)Project funded by China Postdoctoral Science Foundation(2019M6603068)Science Foundation of Peking University Cancer Hospital(2020-16).
文摘Background:Evading immune surveillance is necessary for tumor metastasis.Thus,there is an urgent need to better understand the interaction between metastasis and mechanisms of tumor immune evasion.In this study,we aimed to clarify a novel mechanism that link tumor metastasis and immunosuppression in the development of esophageal squamous cell carcinoma(ESCC).Methods:The expression of melanoma-associated antigen C3(MAGE-C3)was detected using immunohistochemistry.Transwell assays were used to evaluate the migration and invasion ability of esophageal squamous cell carcinoma(ESCC)cells.Metastasis assays in mice were used to evaluate metastatic ability in vivo.Lymphocyte-mediated cytotoxicity assays were performed to visualize the immune suppression function on tumor cells.RNA sequencing was performed to identify differentially expressed genes between MAGE-C3 overexpressing ESCC cells and control cells.Gene ontology(GO)enrichment analyses was performed to identify the most altered pathways influenced by MAGE-C3.The activation of the interferon-γ(IFN-γ)pathway was analyzed using Western blotting,GAS luciferase reporter assays,immunofluorescence,and flow cytometry.The role of MAGE-C3 in the IFN-γpathway was determined by Western blotting and immunoprecipitation.Furthermore,immunohistochemistry and flow cytometry analysis monitored the changes of infiltrated T cell populations in murine lung metastases.Results:MAGE-C3 was overexpressed in ESCC tissues.High expression of MAGE-C3 had a significant association with the risk of lymphatic metastasis and poor survival in patients with ESCC.Functional experiments revealed that MAGE-C3 promoted tumor metastasis by activating the epithelial-mesenchymal transition(EMT).MAGE-C3 repressed antitumor immunity and regulated cytokine secretion of T cells,implying an immunosuppressive function.Mechanistically,MAGE-C3 facilitated IFN-γsignaling and upregulated programmed cell death ligand 1(PDŋL1)by binding with IFN-γreceptor 1(IFNGR1)and strengthening the interaction between IFNGR1
文摘目的检测人脑膜瘤组织中黑色素瘤相关抗原MAGE-D4 m RNA的表达并分析其临床意义。方法采用逆转录-聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)方法,检测36例脑膜瘤组织和8例正常人脑组织中MAGE-D4 m RNA的表达,分析MAGE-D4 m RNA的表达与脑膜瘤患者临床病理特征的关系。结果 MAGE-D4 m RNA在脑膜瘤组织中的阳性表达率为58.33%(21/36),明显高于正常人脑组织中的阳性表达率12.50%(1/8)(P<0.05);脑膜瘤组织中MAGE-D4 m RNA的表达与性别、年龄、肿瘤大小和病理类型等临床病理特征无关(P>0.05)。结论在脑膜瘤组织中MAGE-D4的表达率较高,提示MAGE-D4可能成为脑膜瘤免疫治疗的靶抗原。
