IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses

Cancer Cell. 2015 Sep 14;28(3):296-306. doi: 10.1016/j.ccell.2015.07.014. Epub 2015 Aug 27.


Cytokines play a pivotal role in regulating tumor immunogenicity and antitumor immunity. IL-36γ is important for the IL-23/IL-17-dominated inflammation and anti-BCG Th1 immune responses. However, the impact of IL-36γ on tumor immunity is unknown. Here we found that IL-36γ stimulated CD8(+) T cells, NK cells, and γδ T cells synergistically with TCR signaling and/or IL-12. Importantly, IL-36γ exerted profound antitumor effects in vivo and transformed the tumor microenvironment in favor of tumor eradication. Furthermore, IL-36γ strongly increased the efficacy of tumor vaccination. Moreover, IL-36γ expression inversely correlated with the progression of human melanoma and lung cancer. Our study establishes a role of IL-36γ in promoting antitumor immune responses and suggests its potential clinical translation into cancer immunotherapy.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology
  • Humans
  • Immunotherapy / methods
  • Interleukin-1 / immunology*
  • Interleukin-12 / immunology
  • Killer Cells, Natural / immunology*
  • Lung Neoplasms / immunology
  • Melanoma, Experimental / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Tumor Cells, Cultured
  • Tumor Microenvironment / immunology*


  • Antigens, Neoplasm
  • Cancer Vaccines
  • IL36G protein, human
  • Interleukin-1
  • Receptors, Antigen, T-Cell, gamma-delta
  • Interleukin-12