Cell：科学家阐明癌症免疫监视新机制

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

Saïda Dadi, Sagar Chhangawala, Benjamin M. Whitlock, Ruth A. Franklin, Chong T. Luo, Soyoung A. Oh, Ahmed Toure, Yuri Pritykin, Morgan Huse, Christina S. Leslie, Ming O. Li

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 remains 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, T cell receptor (TCR)αβ, 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 deficiency, 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.