Cytotoxic innate lymphoid cells sense cancer cell-expressed interleukin-15 to suppress human and murine malignancies Journal Article


Authors: Kansler, E. R.; Dadi, S.; Krishna, C.; Nixon, B. G.; Stamatiades, E. G.; Liu, M.; Kuo, F.; Zhang, J.; Zhang, X.; Capistrano, K.; Blum, K. A.; Weiss, K.; Kedl, R. M.; Cui, G.; Ikuta, K.; Chan, T. A.; Leslie, C. S.; Hakimi, A. A.; Li, M. O.
Article Title: Cytotoxic innate lymphoid cells sense cancer cell-expressed interleukin-15 to suppress human and murine malignancies
Abstract: Malignancy can be suppressed by the immune system. However, the classes of immunosurveillance responses and their mode of tumor sensing remain incompletely understood. Here, we show that although clear cell renal cell carcinoma (ccRCC) was infiltrated by exhaustion-phenotype CD8+ T cells that negatively correlated with patient prognosis, chromophobe RCC (chRCC) had abundant infiltration of granzyme A-expressing intraepithelial type 1 innate lymphoid cells (ILC1s) that positively associated with patient survival. Interleukin-15 (IL-15) promoted ILC1 granzyme A expression and cytotoxicity, and IL-15 expression in chRCC tumor tissue positively tracked with the ILC1 response. An ILC1 gene signature also predicted survival of a subset of breast cancer patients in association with IL-15 expression. Notably, ILC1s directly interacted with cancer cells, and IL-15 produced by cancer cells supported the expansion and anti-tumor function of ILC1s in a murine breast cancer model. Thus, ILC1 sensing of cancer cell IL-15 defines an immunosurveillance mechanism of epithelial malignancies. © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
Keywords: genetics; cd8+ t lymphocyte; cd8-positive t-lymphocytes; mouse; animal; animals; mice; breast neoplasms; breast tumor; innate immunity; immunity, innate; lymphocyte; lymphocytes; interleukin 15; granzymes; interleukin-15; granzyme; humans; human; female
Journal Title: Nature Immunology
Volume: 23
Issue: 6
ISSN: 1529-2908
Publisher: Nature Publishing Group  
Date Published: 2022-06-01
Start Page: 904
End Page: 915
Language: English
DOI: 10.1038/s41590-022-01213-2
PUBMED: 35618834
PROVIDER: scopus
PMCID: PMC9202504
DOI/URL:
Notes: Article -- Erratum issued, see DOI: 10.1038/s41590-022-01264-5 -- Export Date: 1 July 2022 -- Source: Scopus
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MSK Authors
  1. Timothy Chan
    310 Chan
  2. Christina Leslie
    161 Leslie
  3. Ming Li
    95 Li
  4. Abraham Ari Hakimi
    264 Hakimi
  5. Saida   Dadi
    8 Dadi
  6. Briana Glyn Nixon
    17 Nixon
  7. Ming Liu
    13 Liu
  8. Fengshen Kuo
    44 Kuo
  9. Chirag Krishna
    19 Krishna
  10. Kyle Blum
    36 Blum
  11. Xian Zhang
    8 Zhang
  12. Kate Weiss
    7 Weiss
  13. Jing Zhang
    2 Zhang