1. Therapeutic targeting of TGF-β in cancer: hacking a master switch of immune suppression
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Jitske van den Bulk, Peter ten Dijke, and Noel F C C de Miranda
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0301 basic medicine ,Immunology & Inflammation ,Integrins ,Angiogenesis ,medicine.medical_treatment ,T cell ,T cells ,combination therapy ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Cancer immunotherapy ,Neoplasms ,medicine ,Tumor Microenvironment ,Animals ,Humans ,Review Articles ,Immune Checkpoint Inhibitors ,checkpoint blockade therapy ,Cancer ,transforming growth factor beta ,cancer immunotherapy ,biology ,business.industry ,General Medicine ,Transforming growth factor beta ,medicine.disease ,Immunity, Innate ,3. Good health ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Cancer research ,Immunotherapy ,business ,tumour microenvironment - Abstract
Cancers may escape elimination by the host immune system by rewiring the tumour microenvironment towards an immune suppressive state. Transforming growth factor-β (TGF-β) is a secreted multifunctional cytokine that strongly regulates the activity of immune cells while, in parallel, can promote malignant features such as cancer cell invasion and migration, angiogenesis, and the emergence of cancer-associated fibroblasts. TGF-β is abundantly expressed in cancers and, most often, its abundance associated with poor clinical outcomes. Immunotherapeutic strategies, particularly T cell checkpoint blockade therapies, so far, only produce clinical benefit in a minority of cancer patients. The inhibition of TGF-β activity is a promising approach to increase the efficacy of T cell checkpoint blockade therapies. In this review, we briefly outline the immunoregulatory functions of TGF-β in physiological and malignant contexts. We then deliberate on how the therapeutic targeting of TGF-β may lead to a broadened applicability and success of state-of-the-art immunotherapies.
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