肺腺癌浸润CD8^(+)T细胞表达CD39的机制  

Mechanism of lung adenocarcinoma-infiltrating CD8^(+)T cells expressing CD39

作　　者：逯君霞 赵彬 侯隽[1] 王良海[1] 吴向未[2] 陈雪玲[1] 许军英 LU Junxia;ZHAO Bin;HOU Jun;WANG Lianghai;WU Xiangwei;CHEN Xueling;XU Junying(Department of Pathogenic Biology and Immunology,School of Medicine,Shihezi University,Shihezi 832000,Xinjiang,China;Department of Hepatobiliary Surgery,the First Affiliated Hospital,School of Medicine,Shihezi University,Shihezi 832000,Xinjiang,China)

机构地区：[1]石河子大学医学院病原生物学与免疫学教研室,新疆石河子832000 [2]石河子大学医学院第一附属医院肝胆外科,新疆石河子832000

出　　处：《中国肿瘤生物治疗杂志》2023年第2期129-134,共6页Chinese Journal of Cancer Biotherapy

基　　金：国家自然地区科学基金(No.82060297);自治区研究生科研创新项目(No.XJ2022G111);石河子大学自主支持科研项目(No.ZZZC202132)。

摘　　要：目的:探讨肿瘤浸润CD8^(+)T细胞表达CD39的可能机制。方法:通过TCGA数据库的肺腺癌(LUAD)组织及正常肺组织转录组数据分析CD39在LUAD组织和正常肺组织中的表达差异及其对患者预后的影响,分析CD39表达与T细胞浸润、激活的关系。用小鼠LUAD Lewis细胞建立小鼠皮下移植瘤模型,FCM检测淋巴结、脾脏以及移植瘤组织中CD8^(+)CD39^(+)T细胞。收集Lewis细胞培养上清液作为条件培养基(CCM),免疫磁珠法(MACS)分选CD8^(+)T细胞、CD11b^(+)细胞;在培养基中分别加入CCM、IL-6和采取非接触或接触培养方式进行培养,探索CD8^(+)T细胞表达CD39的可能机制。结果:CD39在LUAD组织中呈低表达(P<0.01),其表达水平与LUAD患者OS、T细胞浸润和激活水平均呈正相关(P<0.05或P<0.001)。FCM检测结果显示,在移植瘤组织中CD8^(+)CD39^(+)T细胞的比例明显高于淋巴结及脾脏(P<0.01);CCM及IL-6不能直接诱导CD8^(+)T细胞表达CD39,非接触共培养CD11b^(+)细胞与CD8^(+)T细胞也不能诱导CD8^(+)T细胞表达CD39,CD11b^(+)细胞与CD8^(+)T细胞直接接触共培养可诱导CD8^(+)T细胞表达CD39(P<0.01)。结论:CD11b^(+)细胞通过直接接触方式诱导肿瘤浸润CD8^(+)T细胞表达CD39,CD39可能是LUAD特异性CD8^(+)T细胞的分子标志。Objective:To study the possible mechanism of lung adenocarcinoma-infiltrating CD8^(+)T cells expressing CD39.Methods:The transcriptomic data of lung adenocarcinoma(LUAD)tissues and normal lung tissues from the TCGA database were used to analyze the differences in CD39 expression in LUAD tissues and normal lung tissues and its impact on patient prognosis,and to analyze the relationship between CD39 expression and T cell infiltration and activation.Mouse subcutaneous transplantation tumor model was established using LUAD Lewis cells.Flow cytometry was used to detect the expression of CD8^(+)CD39^(+)T cells in lymph nodes,pancreas and transplantation tumor tissues.Lewis cell culture supernatant was collected as conditioned culture medium(CCM).CD8^(+)T cells and CD11b^(+)cells were sorted by magnetic activated cell sorting(MACS).Then,CCM and mouse recombinant interleukin-6(IL-6)were added into the supernatant respectively and contact culture and non-contact culture were carried out to explore the possible mechanism of CD39 expression in CD8^(+)T cells.Result:The expression of CD39 in LUAD tissues was low(P<0.01).Its expression level was all positively correlated with overall survival(OS)of LUAD patients,the infiltration of T cells and the level of activation(P<0.05 or P<0.01).Flow cytometry results showed that the proportion of CD8^(+)CD39^(+)T cells in transplantation tumor tissues was significantly higher than that in lymph nodes and spleen(P<0.01).Both CCM and IL-6 could not induce CD8^(+)T cells to express CD39.Non-contact co-culture of CD11b^(+)cells and CD8^(+)T cells could not induce CD8^(+)T cells to express CD39 either.Direct contact co-culture of CD11b^(+)cells and CD8^(+)T cells could induce CD8^(+)T cells to express CD39(P<0.01).Conclusion:CD11b^(+)cells induced tumor-infiltrating CD8^(+)T cells to express CD39 through direct contact,and CD39 may act as a molecule marker of LUAD-specific CD8^(+)T cells.

关 键 词：肺腺癌 肿瘤浸润CD39 CD11B CD8^(+)T细胞 

分 类 号：R734.2[医药卫生—肿瘤] R730.2[医药卫生—临床医学]