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


ABSTRACT: Since TGF-β was recognized as an essential secreted cytokine in embryogenesis and adult tissue homeostasis a decade ago, our knowledge of the role of TGF-β in mammalian development and disease, particularly cancer, has constantly been updated. Mounting evidence has confirmed that TGF-β is the principal regulator of the immune system, as deprivation of TGF-β signaling completely abrogates adaptive immunity. However, enhancing TGF-β 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-β signaling and the immune system makes it challenging to develop effective monotherapies targeting TGF-β, especially for cancer treatment. Nonetheless, recent work on combination therapies of TGF-β inhibition and immunotherapy have provide insights into the development of TGF-β-targeted therapies, with favorable outcomes in patients with advanced cancer. Hence, we summarize the entanglement between TGF-β and the immune system in the developmental and tumor contexts and recent progress on hijacking crucial TGF-β signaling pathways as an emerging area of cancer therapy.

SUBMITTER: Chen B 

PROVIDER: S-EPMC9204485 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Chen Baode B   Mu Chenglin C   Zhang Zhiwei Z   He Xuelin X   Liu Xia X  

Frontiers in immunology 20220526


Since TGF-β was recognized as an essential secreted cytokine in embryogenesis and adult tissue homeostasis a decade ago, our knowledge of the role of TGF-β in mammalian development and disease, particularly cancer, has constantly been updated. Mounting evidence has confirmed that TGF-β is the principal regulator of the immune system, as deprivation of TGF-β signaling completely abrogates adaptive immunity. However, enhancing TGF-β signaling constrains the immune response through multiple mechani  ...[more]

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