[PDF][PDF] IL-36γ transforms the tumor microenvironment and promotes type 1 lymphocyte-mediated antitumor immune responses

X Wang, X Zhao, C Feng, A Weinstein, R Xia, W Wen… - Cancer cell, 2015 - cell.com
X Wang, X Zhao, C Feng, A Weinstein, R Xia, W Wen, Q Lv, S Zuo, P Tang, X Yang, X Chen…
Cancer cell, 2015cell.com
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 …
Summary
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.
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