TY - JOUR
T1 - Cancer Immunosurveillance by Tissue-Resident Innate Lymphoid Cells and Innate-like T Cells
AU - Dadi, Saïda
AU - Chhangawala, Sagar
AU - Whitlock, Benjamin M.
AU - Franklin, Ruth A.
AU - Luo, Chong T.
AU - Oh, Soyoung A.
AU - Toure, Ahmed
AU - Pritykin, Yuri
AU - Huse, Morgan
AU - Leslie, Christina S.
AU - Li, Ming O.
N1 - Funding Information:
We thank P. Rothman for providing the Nfil3 −/− mouse strain, Y. Tagaya and T. Waldmann for providing the IL-15 Transgenic mouse strain, and N. Cheung for the IL-15/IL-15Rα complex. We also thank the M. Li lab for insightful discussions. MSKCC has filed a provisional patent application with the U.S. Patent and Trademark Office towards methods and compositions for cancer immunotherapy targeting innate lymphoid cells and innate-like T cells. S.D. and M.O.L. are listed as inventors on this patent application. This work was supported by the Ludwig Center for Cancer Immunology (M.O.L.) and the Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748).
Funding Information:
We thank P. Rothman for providing the Nfil3
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/1/28
Y1 - 2016/1/28
N2 - Summary 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.
AB - Summary 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.
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U2 - 10.1016/j.cell.2016.01.002
DO - 10.1016/j.cell.2016.01.002
M3 - Article
C2 - 26806130
AN - SCOPUS:84955561954
SN - 0092-8674
VL - 164
SP - 365
EP - 377
JO - Cell
JF - Cell
IS - 3
ER -