Cancer Immunosurveillance by Innate Lymphoid Cells and Innate-like T Cells

Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remain obscure. Here we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, TCRaß and TCR?d lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a and CD103, these cells share a gene expression signature distinct from those of conventional NK cells, T cells and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor-infiltrating NK cells; and IL-15, but not Nfil3, deficiency results in accelerated tumor growth. These findings reveal a novel tumor-elicited cancer immunosurveillance mechanism that engages unconventional type 1-like innate lymphoid cells and type 1 innate-like T cells. Overall design: Total 11 samples were analyzed. 2 replicates per sample.

免疫系统可通过一种被称为免疫监视（immunosurveillance）的过程抑制恶性肿瘤的发生发展。然而，免疫监视在自发性肿瘤中的作用范围，以及其所涉及的细胞类型组成，目前仍不明确。本研究显示，在癌基因诱导的小鼠癌症模型中，细胞转化可触发组织驻留淋巴细胞应答反应。源自先天免疫、TCRαβ和TCRγδ谱系的非循环细胞毒性淋巴细胞，会在早期肿瘤中发生扩增。这类细胞以高表达NK1.1、CD49a及CD103为特征，其基因表达特征与常规NK细胞、T细胞及恒定自然杀伤T细胞（invariant NKT cells）均不相同。这类淋巴细胞的生成依赖于细胞因子IL-15，而非肿瘤浸润NK细胞分化所必需的转录因子Nfil3；且IL-15（而非Nfil3）缺陷会导致肿瘤生长加速。本研究发现了一种全新的肿瘤诱导性癌症免疫监视机制，该机制涉及非经典的1型样先天淋巴细胞及1型先天样T细胞。实验整体设计：本研究共分析11份样本，每份样本设置2次生物学重复。