CD8+ CD103+ Tumor-Infiltrating Lymphocytes Are Tumor-Specific Tissue-Resident Memory T Cells and a Prognostic Factor for Survival in Lung Cancer Patients
CD8+ CD103+ Tumor-Infiltrating Lymphocytes Are Tumor-Specific Tissue-Resident Memory T Cells and a Prognostic Factor for Survival in Lung Cancer Patients
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DOI：
10.4049/jimmunol.1402711
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发表时间：
2015-04-01
影响因子：
4.4
通讯作者：
Mami-Chouaib, Fathia
中科院分区：
文献类型：
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作者：
Djenidi, Faycal;Adam, Julien;Mami-Chouaib, Fathia
我们先前已经证明了CD103整合素在肺肿瘤浸润性淋巴细胞(TIL)克隆促进特异性TCR介导的上皮性肿瘤细胞杀伤中的作用。然而，CD103在非小细胞肺癌(NSCLC)中对瘤内T细胞分布和功能的影响以及TIL亚群的预后意义尚未得到系统研究。在这项研究中，我们证明了CD103(+)TIL亚群的增强与早期NSCLC患者生存率的改善和上皮内淋巴细胞浸润的增加相关。此外，我们的结果表明，新鲜从NSCLC标本中分离的CD8(+)CD103(+)TIL表现出组织驻留记忆T细胞的转录和表型特征，并频繁表达PD-1和TIM-3检查点受体。这个TIL亚群还表现出激活诱导的细胞死亡增加，并在阻断PD-1-PD-L1相互作用后介导对自体肿瘤细胞的特异性细胞杀伤活性。这些发现强调了CD8(+)CD103(+)组织驻留记忆T细胞在促进肿瘤内CTL反应中的作用，并支持在NSCLC患者中使用抗PD-1阻断抗体来逆转肿瘤诱导的T细胞耗竭的理论基础。
We had previously demonstrated the role of CD103 integrin on lung tumor-infiltrating lymphocyte (TIL) clones in promoting specific TCR-mediated epithelial tumor cell cytotoxicity. However, the contribution of CD103 on intratumoral T cell distribution and functions and the prognosis significance of TIL subpopulations in non-small cell lung carcinoma (NSCLC) have thus far not been systematically addressed. In this study, we show that an enhanced CD103(+) TIL subset correlates with improved early stage NSCLC patient survival and increased intraepithelial lymphocyte infiltration. Moreover, our results indicate that CD8(+) CD103(+) TIL, freshly isolated from NSCLC specimens, display transcriptomic and phenotypic signatures characteristic of tissue-resident memory T cells and frequently express PD-1 and Tim-3 checkpoint receptors. This TIL subset also displays increased activation-induced cell death and mediates specific cytolytic activity toward autologous tumor cells upon blockade of the PD-1-PD-L1 interaction. These findings emphasize the role of CD8(+) CD103(+) tissue-resident memory T cells in promoting intratumoral CTL responses and support the rationale for using anti-PD-1 blocking Ab to reverse tumor-induced T cell exhaustion in NSCLC patients.