CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer.
CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer.
复制标题
CD8 CD39 T 细胞介导膀胱癌的抗肿瘤细胞毒性
DOI：
10.2147/ott.s297272
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发表时间：
2021
影响因子：
4
通讯作者：
Yang R
中科院分区：
文献类型：
--
作者：
Zhu W;Zhao Z;Feng B;Yu W;Li J;Guo H;Yang R
虽然免疫疗法在部分膀胱癌（BLCA）患者中效果良好，但其抗PD-1抑制剂的总体应答率仍不令人满意。此外，越来越多的证据表明，肿瘤浸润淋巴细胞（TILs）免疫疗法在各种癌症中表现出良好的疗效。鉴于BLCA的巨大异质性和较低的总生存率，迫切需要探索新的免疫检查点（IC）或TILs疗法来改善BLCA患者的生存预后。材料与方法利用公共生物信息学数据库，对5个潜在的ICs靶点（TIM-3、LAG-3、OX 40、4-1BB和CD 39）的预后价值进行分析。本研究共纳入2020年5月至2020年10月在我院接受手术治疗的46例BLCA患者。采用流式细胞术检测BLCA患者T细胞中PD-1、TIM-3、LAG-3、OX 40、4-1BB和CD 39的表达，分析不同T细胞亚群与临床病理参数的相关性。此外，分选小鼠CD 4 + CD 39 + T细胞、CD 4 + CD 39- T细胞、CD 8 + CD 39 + T细胞和CD 8 + CD 39- T细胞，并与MB 49膀胱癌细胞系体外共培养，以研究肿瘤反应性TILs的潜在生物标志物。结果公共生物信息学数据库分析显示，只有CD 39的高表达与晚期肿瘤的临床分期显著相关（P < 0.001），并有降低生存率的趋势。CD 4 +/CD 8 + T细胞中CD 39的高表达与病理T分期（pT <2，P = 0.041）和乳头状瘤（P = 0.038）显著相关。此外，CD 8 + CD 39 + T细胞显示出更强的肿瘤杀伤作用，并产生比其他T细胞群体更高水平的IFN-γ。结论CD 39可能是BLCA的一个潜在预后指标，CD 8 + CD 39 + T细胞可作为TIL治疗的肿瘤反应性和杀伤性T细胞。
Introduction Although immunotherapy works well in parts of patients with bladder cancer (BLCA), its overall response rate of anti-PD-1 inhibitors remains unsatisfactory. Besides, growing evidence shows that tumor-infiltrating lymphocytes (TILs) immunotherapy has demonstrated excellent efficacy in various cancers. Considering the huge heterogeneity and low overall survival rate of BLCA, it is urgent to explore the new immune checkpoints (ICs) or TILs therapy to improve the survival prognosis for BLCA patients. Materials and Methods The public bioinformatics databases were used to explore the prognostic value of 5 potential ICs targets (TIM-3, LAG-3, OX40, 4–1BB and CD39). A total of 46 BLCA patients undergoing surgical treatment at our hospital from May 2020 to October 2020 were enrolled in this study. The expressions of PD-1, TIM-3, LAG-3, OX40, 4–1BB, and CD39 in T cells of BLCA patients were explored by flow cytometry, and the correlation between different subgroups of T cells and clinicopathological parameters was analyzed. Besides, the mouse CD4+CD39+ T cells, CD4+CD39- T cells, CD8+CD39+ T cells, and CD8+CD39- T cells were sorted and co-cultured with MB49 bladder cancer cell lines in vitro to investigate the potential biomarker of tumor-reactive TILs. Results Public bioinformatics databases analyses show that only the high expression of CD39 was significantly associated with advanced tumor stage (P < 0.001) and tend to result in a worse survival rate. In our study, the elevated expression of CD39 in CD4+/CD8+ T cells were significantly associated with the pathological T stage (pT <2, P = 0.041) and papillary tumor (P = 0.038). Moreover, the CD8+CD39+ T cells showed a stronger tumor-killing effect and produced a higher level of IFN-γ than other T cell populations. Conclusion CD39 may be a potential prognostic marker in BLCA, and CD8+CD39+ T cells may be selected as tumor-reactive and killing T cells for TILs therapy.