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

Cell. 2016 Jan 28;164(3):365-77. doi: 10.1016/j.cell.2016.01.002. Epub 2016 Jan 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Granzymes / metabolism
  • Interleukin-15 / immunology
  • Lymphocytes / immunology*
  • Mammary Neoplasms, Experimental / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Monitoring, Immunologic*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • T-Lymphocyte Subsets / immunology*


  • Basic-Leucine Zipper Transcription Factors
  • Interleukin-15
  • Nfil3 protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • Granzymes