Therapeutic targeting of TGF-β in cancer: hacking a master switch of immune suppression

Cancers may escape elimination by the host immune system by rewiring the tumour microenvironment towards an immune suppressive state. Transforming growth factor-beta (TGF-beta) 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-beta 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-beta 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-beta in physiological and malignant contexts. We then deliberate on how the therapeutic targeting of TGF-beta may lead to a broadened applicability and success of state-of-the-art immunotherapies.

Automated summary

TGF-beta plays a crucial role in regulating immune cell activity and promoting malignant features in cancer. Targeting TGF-beta therapeutically may enhance the success of immunotherapies.