TGFβ: Signaling Blockade for Cancer Immunotherapy.

Autor: Chen SY; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA., Mamai O; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA., Akhurst RJ; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.; Department of Anatomy, University of California, San Francisco, California, USA.
Jazyk: angličtina
Zdroj: Annual review of cancer biology [Annu Rev Cancer Biol] 2022; Vol. 6 (1), pp. 123-146. Date of Electronic Publication: 2021 Dec 22.
DOI: 10.1146/annurev-cancerbio-070620-103554
Abstrakt: Discovered over four decades ago, transforming growth factor β (TGFβ) is a potent pleiotropic cytokine that has context-dependent effects on most cell types. It acts as a tumor suppressor in some cancers and/or supports tumor progression and metastasis through its effects on the tumor stroma and immune microenvironment. In TGFβ-responsive tumors it can promote invasion and metastasis through epithelial-mesenchymal transformation, the appearance of cancer stem cell features, and resistance to many drug classes, including checkpoint blockade immunotherapies. Here we consider the biological activities of TGFβ action on different cells of relevance toward improving immunotherapy outcomes for patients, with a focus on the adaptive immune system. We discuss recent advances in the development of drugs that target the TGFβ signaling pathway in a tumor-specific or cell type-specific manner to improve the therapeutic window between response rates and adverse effects.
Databáze: MEDLINE