The Love-Hate Relationship Between TGF-β Signaling and the Immune System During Development and Tumorigenesis

被引：28

作者：

Chen, Baode ^{[1
]}

Mu, Chenglin ^{[2
]}

Zhang, Zhiwei ^{[2
]}

He, Xuelin ^{[3
]}

Liu, Xia ^{[2
]}

机构：

[1] Zhejiang Univ, Affiliated Hosp 1, Coll Med, Dept Lab Med, Hangzhou, Peoples R China

[2] Zhejiang Univ ZJU Hangzhou Global Sci, Inst Intelligent Bio Chem Mfg iBCM, Technol Innovat Ctr, Hangzhou, Peoples R China

[3] Zhejiang Univ, Affiliated Hosp 1, Coll Med, Kidney Dis Ctr, Hangzhou, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷

关键词：

TGF-beta; immune system; tumor progression; tumor microenvironment; cancer therapy; GROWTH-FACTOR-BETA; HEMATOPOIETIC STEM-CELLS; T-CELL; TRANSFORMING GROWTH-FACTOR-BETA-1; MYELOID CELLS; TUMOR-GROWTH; NK CELLS; CANCER; RECEPTOR; EXPRESSION;

D O I：

10.3389/fimmu.2022.891268

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Since TGF-beta was recognized as an essential secreted cytokine in embryogenesis and adult tissue homeostasis a decade ago, our knowledge of the role of TGF-beta in mammalian development and disease, particularly cancer, has constantly been updated. Mounting evidence has confirmed that TGF-beta is the principal regulator of the immune system, as deprivation of TGF-beta signaling completely abrogates adaptive immunity. However, enhancing TGF-beta signaling constrains the immune response through multiple mechanisms, including boosting Treg cell differentiation and inducing CD8(+) T-cell apoptosis in the disease context. The love-hate relationship between TGF-beta signaling and the immune system makes it challenging to develop effective monotherapies targeting TGF-beta, especially for cancer treatment. Nonetheless, recent work on combination therapies of TGF-beta inhibition and immunotherapy have provide insights into the development of TGF-beta-targeted therapies, with favorable outcomes in patients with advanced cancer. Hence, we summarize the entanglement between TGF-beta and the immune system in the developmental and tumor contexts and recent progress on hijacking crucial TGF-beta signaling pathways as an emerging area of cancer therapy.

引用

页数：17

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