Department of Thoracic Surgery, Tong Ji Medical School, Huazhong University of Science and Technology, China; Laboratory of Thoracic Surgery, Tong Ji Hospital, Tong Ji Medical School, Huazhong University of Science and Technology, China.
Laboratory of Cell Engineering, Tong Ji Medical School, Huazhong University of Science and Technology, China.
Cell Immunol. 2018 Mar;325:48-55. doi: 10.1016/j.cellimm.2018.02.002. Epub 2018 Feb 7.
CD103CD8 tumor infiltrating lymphocytes (TILs) have been linked to prolonged survival in various types of cancer including non-small cell lung cancer (NSCLC). However, the factors associated with the retention of CD103CD8 TILs in lung cancer tissues remain largely unknown. Additionally, the contribution of CD103CD8 TILs to effective PD-1 based immunotherapy has not been fully elucidated. In this study, we identified that the expression levels of E-cadherin and TGF-β were significantly correlated with the distribution and the density of CD103 TILs in lung cancer tumor tissues. Unexpectedly, we observed that CD103CD8 TILs that expressed higher levels of PD-1 co-express Ki-67. Moreover, CD103CD8 TILs expressed an increased level of T-bet compared to their counterparts, indicating these cells may be better armed for immunotherapy. Lastly, PD-1 pathway blockade led to a significantly increased production of IFN-γ by CD103CD8 TILs, suggesting CD103CD8 TILs could serve as a predictive biomarker for PD-1 based immunotherapy.
CD103+CD8+肿瘤浸润淋巴细胞（TILs）与多种癌症（包括非小细胞肺癌（NSCLC））患者的生存期延长相关。然而，与肺癌组织中 CD103+CD8+TILs 保留相关的因素在很大程度上仍不清楚。此外，CD103+CD8+TILs 对有效的 PD-1 为基础的免疫治疗的贡献也尚未完全阐明。在本研究中，我们发现 E-钙黏蛋白和 TGF-β的表达水平与肺癌肿瘤组织中 CD103+TILs 的分布和密度显著相关。出乎意料的是，我们观察到表达更高水平 PD-1 的 CD103+CD8+TILs 共同表达 Ki-67。此外，与对照组相比，CD103+CD8+TILs 表达了更高水平的 T-bet，表明这些细胞可能更适合免疫治疗。最后，PD-1 通路阻断导致 CD103+CD8+TILs 产生 IFN-γ 的显著增加，提示 CD103+CD8+TILs 可作为 PD-1 为基础免疫治疗的预测生物标志物。
