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

Xuefeng Wang; Xin Zhao; Chao Feng; Aliyah Weinstein; Rui Xia; Wen Wen; Quansheng Lv; Shuting Zuo; Peijun Tang; Xi Yang; Xiaojuan Chen; Hongrui Wang; Shayang Zang; Lindsay Stollings; Timothy L. Denning; Jingting Jiang; Jie Fan; Guangbo Zhang; Xueguang Zhang; Yibei Zhu; Walter Storkus; Binfeng Lu

doi:10.1016/j.ccell.2015.07.014

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

Xuefeng Wang
, Xin Zhao
, Chao Feng
, Aliyah Weinstein
, Rui Xia
, Wen Wen
, Quansheng Lv
, Shuting Zuo
, Peijun Tang
, Xi Yang
, Xiaojuan Chen
, Hongrui Wang
, Shayang Zang
, Lindsay Stollings
, Timothy L. Denning
, Jingting Jiang
, Jie Fan
, Guangbo Zhang
, Xueguang Zhang
, Yibei Zhu

Walter Storkus, Binfeng Lu

Center for Discovery and Innovation

University of Pittsburgh
Soochow University
The First Affiliated Hospital of Soochow University
Jilin University
Fifth People's Hospital of Suzhou
Tsinghua University
Xiamen University
Georgia State University
The Third Affiliated Hospital of Soochow University
VA Medical Center

Research output: Contribution to journal › Article › peer-review

107 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	296-306
Number of pages	11
Journal	Cancer Cell
Volume	28
Issue number	3
DOIs	https://doi.org/10.1016/j.ccell.2015.07.014
State	Published - 14 Sep 2015

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SDG 3 Good Health and Well-being

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10.1016/j.ccell.2015.07.014

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Wang, X., Zhao, X., Feng, C., Weinstein, A., Xia, R., Wen, W., Lv, Q., Zuo, S., Tang, P., Yang, X., Chen, X., Wang, H., Zang, S., Stollings, L., Denning, T. L., Jiang, J., Fan, J., Zhang, G., Zhang, X., ... Lu, B. (2015). IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses. Cancer Cell, 28(3), 296-306. https://doi.org/10.1016/j.ccell.2015.07.014

@article{a35bfdb14d8a4627b4290a14ad0cd3e5,

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

abstract = "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.",

author = "Xuefeng Wang and Xin Zhao and Chao Feng and Aliyah Weinstein and Rui Xia and Wen Wen and Quansheng Lv and Shuting Zuo and Peijun Tang and Xi Yang and Xiaojuan Chen and Hongrui Wang and Shayang Zang and Lindsay Stollings and Denning, \{Timothy L.\} and Jingting Jiang and Jie Fan and Guangbo Zhang and Xueguang Zhang and Yibei Zhu and Walter Storkus and Binfeng Lu",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = sep,

day = "14",

doi = "10.1016/j.ccell.2015.07.014",

language = "English",

volume = "28",

pages = "296--306",

journal = "Cancer Cell",

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}

Wang, X, Zhao, X, Feng, C, Weinstein, A, Xia, R, Wen, W, Lv, Q, Zuo, S, Tang, P, Yang, X, Chen, X, Wang, H, Zang, S, Stollings, L, Denning, TL, Jiang, J, Fan, J, Zhang, G, Zhang, X, Zhu, Y, Storkus, W & Lu, B 2015, 'IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses', Cancer Cell, vol. 28, no. 3, pp. 296-306. https://doi.org/10.1016/j.ccell.2015.07.014

TY - JOUR

T1 - IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses

AU - Wang, Xuefeng

AU - Zhao, Xin

AU - Feng, Chao

AU - Weinstein, Aliyah

AU - Xia, Rui

AU - Wen, Wen

AU - Lv, Quansheng

AU - Zuo, Shuting

AU - Tang, Peijun

AU - Yang, Xi

AU - Chen, Xiaojuan

AU - Wang, Hongrui

AU - Zang, Shayang

AU - Stollings, Lindsay

AU - Denning, Timothy L.

AU - Jiang, Jingting

AU - Fan, Jie

AU - Zhang, Guangbo

AU - Zhang, Xueguang

AU - Zhu, Yibei

AU - Storkus, Walter

AU - Lu, Binfeng

PY - 2015/9/14

Y1 - 2015/9/14

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84942365848

U2 - 10.1016/j.ccell.2015.07.014

DO - 10.1016/j.ccell.2015.07.014

M3 - Article

C2 - 26321222

AN - SCOPUS:84942365848

SN - 1535-6108

VL - 28

SP - 296

EP - 306

JO - Cancer Cell

JF - Cancer Cell

IS - 3

ER -

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

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