Cancer Immunosurveillance by Tissue-Resident Innate Lymphoid Cells and Innate-like T Cells.
Cancer Immunosurveillance by Tissue-Resident Innate Lymphoid Cells and Innate-like T Cells.
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DOI：
10.1016/j.cell.2016.01.002
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发表时间：
2016-01-28
期刊：
影响因子：
64.5
通讯作者：
Li MO
中科院分区：
文献类型：
--
作者：
Dadi S;Chhangawala S;Whitlock BM;Franklin RA;Luo CT;Oh SA;Toure A;Pritykin Y;Huse M;Leslie CS;Li MO
在称为免疫监视的过程中，免疫系统可以抑制细胞增殖。然而，在自发性癌症中发生免疫监视的程度以及参与细胞类型的组成仍然不清楚。在这里，我们表明，细胞转化触发癌基因诱导的小鼠癌症模型中的组织驻留淋巴细胞反应。源自先天性TCRαβ和TCRγδ谱系的非循环细胞毒性淋巴细胞在早期肿瘤中扩增。这些细胞以NK1.1、CD 49 a和CD 103的高表达为特征，具有与常规NK细胞、T细胞和不变NKT细胞不同的基因表达特征。这些淋巴细胞的产生依赖于细胞因子IL-15，而不是肿瘤浸润NK细胞分化所需的转录因子Nfil 3，并且IL-15而不是Nfil 3缺乏导致肿瘤生长加速。这些发现揭示了肿瘤引起的免疫监视机制，该机制涉及非常规的1型先天性淋巴样细胞和1型先天性T细胞。
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, TCRαβ and TCRγδ 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 tumor-elicited immunosurveillance mechanism that engages unconventional type 1-like innate lymphoid cells and type 1 innate-like T cells.