Poor clinical outcomes and immunoevasive contexture in CXCL13+CD8+ T cells enriched gastric cancer patients.
Poor clinical outcomes and immunoevasive contexture in CXCL13+CD8+ T cells enriched gastric cancer patients.
复制标题
CXCL13 CD8 T 细胞富集的胃癌患者的临床结果不佳和免疫逃避环境
DOI：
10.1080/2162402x.2021.1915560
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发表时间：
2021-04-27
期刊：
影响因子：
7.2
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Jin K;Cao Y;Gu Y;Fang H;Fei Y;Wang J;Liu X;Lv K;He X;Lin C;Liu H;Li H;He H;Li R;Zhang H;Xu J
趋化因子（C-X-C基序）配体13（CXCL 13）作为一种不良的生存预测因子，在几种类型的恶性肿瘤中已被研究。CXCL 13在滤泡辅助性T细胞（TFH）中的分泌和生理作用已被充分描述，而CD 8+肿瘤浸润淋巴细胞（TILs）相关的CXCL 13的临床意义仍然未知。本研究旨在探讨CXCL 13 + CD 8 + T细胞在胃癌患者生存和化疗反应预测中的临床意义。本研究选取440例来自中山医院的肿瘤微阵列（TMA）标本，随机分为检验集（n = 220）和验证集（n = 220）进行分析。免疫组化法检测CXCL 13 + CD 8 + T细胞。另取60例胃癌患者的新鲜肿瘤组织，采用流式细胞术（FCM）检测CXCL 13 + CD 8 + T细胞功能状态。我们发现，高肿瘤内CXCL 13 + CD 8 + T细胞浸润预测胃癌的总体生存率和化疗反应性较差。CXCL 13 + CD 8 +T细胞与免疫逃避性结构相关，具有增加的调节性T（Treg）细胞和功能失调的细胞毒性T淋巴细胞（CTL）。此外，CXCL 13 + CD 8 + T细胞和CD 8 + T细胞浸润的组合分析将患者分为具有不同临床结果和化疗反应性的不同风险组。结论：CXCL 13 + CD 8 + T细胞浸润可作为胃癌患者预后的独立预测指标。CXCL 13 + CD 8 + T细胞是一个耗竭的CD 8 + T细胞亚群，可能是胃癌免疫治疗的潜在靶点。
As an adverse survival prognosticator, chemokine (C-X-C motif) ligand 13 (CXCL13) has been studied in several types of malignancies. The secretion and physiological roles of CXCL13 in follicular helper T cells (TFH) cells have been well described, while the clinical significance of CD8+ tumor-infiltrating lymphocytes (TILs)-associated CXCL13 remains unknown. This study aims to investigate the clinical significance of CXCL13+CD8+ T cells in survival and chemotherapeutic responsiveness prediction in gastric cancer. In this study, 440 patients enrolled from Zhongshan Hospital with tumor microarray (TMA) specimens were randomly divided into testing set (n = 220) and validation set (n = 220) for analysis. CXCL13+CD8+ T cells were detected by multicolor immunohistochemistry. Fresh tumor tissue samples from another 60 gastric cancer patients were collected to detect CXCL13+CD8+ T cells functional status by flow cytometry (FCM). We found that high intratumoral CXCL13+CD8+ T cells infiltration predicted poor overall survival and inferior chemotherapeutic responsiveness in gastric cancer. CXCL13+CD8+T cells were associated with immunoevasive contexture with increased regulatory T (Treg) cells and dysfunctional cytotoxic T lymphocytes (CTLs). Moreover, the combinational analysis of CXCL13+CD8+ T cells and CD8+ T cells infiltration stratified patients into distinct risk groups with different clinical outcomes and chemotherapeutic responsiveness. Conclusively, intratumoral CXCL13+CD8+ T cells infiltration could be an independent prognostic and predictive marker for gastric cancer patients. CXCL13+CD8+ T cells represented an exhausted CD8+ T cell subset, and might be a potential immunotherapeutic target in gastric cancer.