Tumor promoting roles of IL-10, TGF-β, IL-4, and IL-35: Its implications in cancer immunotherapy

被引:155
作者
Mirlekar, Bhalchandra [1 ]
机构
[1] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA
关键词
Immune-suppressive cytokines; tumor microenvironment; cancer immunotherapy; antitumor immunity; tumor growth; GROWTH-FACTOR-BETA; REGULATORY T-CELLS; HUMAN MONOCLONAL-ANTIBODY; BREAST-CANCER; IL-4-PSEUDOMONAS EXOTOXIN; CLINICAL DEVELOPMENT; CYTOKINE EXPRESSION; INTERLEUKIN-4; IL-4; ANTITUMOR IMMUNITY; SUPPRESSOR-CELLS;
D O I
10.1177/20503121211069012
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cytokines play a critical role in regulating host immune response toward cancer and determining the overall fate of tumorigenesis. The tumor microenvironment is dominated mainly by immune-suppressive cytokines that control effector antitumor immunity and promote survival and the proliferation of cancer cells, which ultimately leads to enhanced tumor growth. In addition to tumor cells, the heterogeneous immune cells present within the tumor milieu are the significant source of immune-suppressive cytokines. These cytokines are classified into a broad range; however, in most tumor types, the interleukin-10, transforming growth factor-beta, interleukin-4, and interleukin-35 are consistently reported as immune-suppressive cytokines that help tumor growth and metastasis. The most emerging concern in cancer treatment is hijacking and restraining the activity of antitumor immune cells in the tumor niche due to a highly immune-suppressive environment. This review summarizes the role and precise functions of interleukin-10, transforming growth factor-0, interleukin-4, and interleukin-35 in modulating tumor immune contexture and its implication in developing effective immune-therapeutic approaches. Concise conclusion Recent effort geared toward developing novel immune-therapeutic approaches faces significant challenges due to sustained mutations in tumor cells and a highly immune-suppressive microenvironment present within the tumor milieu. The cytokines play a crucial role in developing an immune-suppressive environment that ultimately dictates the fate of tumorigenesis. This review critically covers the novel aspects of predominant immune-suppressive cytokines such as interleukin-10, transforming growth factor-beta, interleukin-4, and interleukin-35 in dictating the fate of tumorigenesis and how targeting these cytokines can help the development of better immune-therapeutic drug regimens for the treatment of cancer.
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页数:15
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共 182 条
[71]   Follicular regulatory T cells infiltrated the ovarian carcinoma and resulted in CD8 T cell dysfunction dependent on IL-10 pathway [J].
Li, Li ;
Ma, Yan ;
Xu, Yuan .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2019, 68 :81-87
[72]   Effects of immune cells and cytokines on inflammation and immunosuppression in the tumor microenvironment [J].
Li, Lihong ;
Yu, Rui ;
Cai, Tiange ;
Chen, Zhen ;
Lan, Meng ;
Zou, Tengteng ;
Wang, Bingyue ;
Wang, Qi ;
Zhao, Yiye ;
Cai, Yu .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2020, 88
[73]   Low-Dose Anti-Angiogenic Therapy Sensitizes Breast Cancer to PD-1 Blockade [J].
Li, Qian ;
Wang, Yifan ;
Jia, Weijuan ;
Deng, Heran ;
Li, Guangdi ;
Deng, Weiye ;
Chen, Jiewen ;
Kim, Betty Y. S. ;
Jiang, Wen ;
Liu, Qiang ;
Liu, Jieqiong .
CLINICAL CANCER RESEARCH, 2020, 26 (07) :1712-1724
[74]   Lauren classification identifies distinct prognostic value and functional status of intratumoral CD8+T cells in gastric cancer [J].
Li, Ruochen ;
Zhang, Heng ;
Cao, Yifan ;
Liu, Xin ;
Chen, Yifan ;
Qi, Yangyang ;
Wang, Jieti ;
Yu, Kuan ;
Lin, Chao ;
Liu, Hao ;
He, Hongyong ;
Li, He ;
Chen, Lingli ;
Shen, Zhenbin ;
Qin, Jing ;
Zhang, Weijuan ;
Sun, Yihong ;
Xu, Jiejie .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2020, 69 (07) :1327-1336
[75]   Endogenous Interleukin-4 Promotes Tumor Development by increasing Tumor Cell Resistance to Apoptosis [J].
Li, Zhiguang ;
Jiang, Jing ;
Wang, Zibing ;
Zhang, Jinhua ;
Xiao, Mingjie ;
Wang, Chunhui ;
Lu, Yu ;
Qin, Zhihai .
CANCER RESEARCH, 2008, 68 (21) :8687-8694
[76]   Paradoxical Roles of IL-4 in Tumor Immunity [J].
Li, Zhiguang ;
Chen, Lin ;
Qin, Zhihai .
CELLULAR & MOLECULAR IMMUNOLOGY, 2009, 6 (06) :415-422
[77]   The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells [J].
Lindau, Dennis ;
Gielen, Paul ;
Kroesen, Michiel ;
Wesseling, Pieter ;
Adema, Gosse J. .
IMMUNOLOGY, 2013, 138 (02) :105-115
[78]   TGF-β suppresses type 2 immunity to cancer [J].
Liu, Ming ;
Kuo, Fengshen ;
Capistrano, Kristelle J. ;
Kang, Davina ;
Nixon, Briana G. ;
Shi, Wei ;
Chou, Chun ;
Do, Mytrang H. ;
Stamatiades, Efstathios G. ;
Gao, Shengyu ;
Li, Shun ;
Chen, Yingbei ;
Hsieh, James J. ;
Hakimi, A. Ari ;
Taniuchi, Ichiro ;
Chan, Timothy A. ;
Li, Ming O. .
NATURE, 2020, 587 (7832) :115-+
[79]   Combined blockade of TGf-β1 and GM-CSF improves chemotherapeutic effects for pancreatic cancer by modulating tumor microenvironment [J].
Liu, Qiaofei ;
Wu, Huanwen ;
Li, Yuan ;
Zhang, Ronghua ;
Kleeff, Jorg ;
Zhang, Xiang ;
Cui, Ming ;
Liu, Jingkai ;
Li, Tong ;
Gao, Junyi ;
Pan, Boju ;
Wu, Wenming ;
Wang, Weibin ;
Zhou, Li ;
Guo, Junchao ;
Dai, Menghua ;
Zhang, Taiping ;
Liao, Quan ;
Lu, Zhaohui ;
Zhao, Yupei .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2020, 69 (08) :1477-1492
[80]   Overcoming original antigenic sin to generate new CD8 T cell IFN-γ responses in an antigen-experienced host [J].
Liu, Xiao Song ;
Dyer, Joanne ;
Leggatt, Graham R. ;
Fernando, Germain J. P. ;
Zhong, Jie ;
Thomas, Ranjeny ;
Frazer, Ian H. .
JOURNAL OF IMMUNOLOGY, 2006, 177 (05) :2873-2879