title: Cancer Immunosurveillance by Tissue-Resident Innate Lymphoid Cells and Innate-like T Cells.
abstract: 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.
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Saïda
authors.initials: S
authors.lastname: Dadi
authors.affiliation: Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Physiology Biophysics and Systems Biology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.
authors.forename: Sagar
authors.initials: S
authors.lastname: Chhangawala
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Biochemistry & Structural Biology, Cell & Developmental Biology, and Molecular Biology Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Whitlock
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Graduate Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Franklin
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Chong T
authors.initials: CT
authors.lastname: Luo
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Soyoung A
authors.initials: SA
authors.lastname: Oh
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Toure
authors.affiliation: Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Pritykin
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Morgan
authors.initials: M
authors.lastname: Huse
authors.affiliation: Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Leslie
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: lim@mskcc.org.
authors.forename: Ming O
authors.initials: MO
authors.lastname: Li
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D053804:Granzymes / Q000378:metabolism; D019409:Interleukin-15 / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015166:Monitoring, Immunologic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D019409:Interleukin-15; C497441:Nfil3 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D053804:Granzymes