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

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

SUBMITTER: van den Bulk J

PROVIDER: S-EPMC7796313 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

van den Bulk Jitske J de Miranda Noel F C C NFCC Ten Dijke Peter P

Clinical science (London, England : 1979) 20210101 1

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 asso ...[more]

PMID: 33399850

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Project description:Influenza is a contagion that has plagued mankind for many decades, and continues to pose concerns every year, with millions of infections globally. The frequent mutations and recombination of the influenza A virus (IAV) cast a looming threat that antigenically novel strains/subtypes will rise with unpredictable pathogenicity and fear of it evolving into a pandemic strain. There have been four major influenza pandemics, since the beginning of twentieth century, with the great 1918 pandemic being the most severe, killing more than 50 million people worldwide. The mechanisms of IAV infection, host immune responses, and how viruses evade from such defensive responses at the molecular and structural levels have been greatly investigated in the past 30?years. While this has advanced our understanding of virus-host interactions and human immunology, and has led to the development of several antiviral drugs, they have minimal impact on the clinical outcomes of infection. The heavy use of these drugs has also imposed selective pressure on IAV to evolve and develop resistance. Vaccination remains the cornerstone of public health efforts to protect against influenza; however, rapid mass-production of sufficient vaccines is unlikely to occur immediately after the beginning of a pandemic. This, therefore, requires novel therapeutic strategies against this continually emerging infectious virus with higher specificity and cross-reactivity against multiple strains/subtypes of IAVs. This review discusses essential virulence factors of IAVs that determine sustainable human-to-human transmission, the mechanisms of viral hijacking of host cells and subversion of host innate immune responses, and novel therapeutic interventions that demonstrate promising antiviral properties against IAV. This hopefully will promote discussions and investigations on novel avenues of prevention and treatment strategies of influenza, that are effective and cross-protective against multiple strains/subtypes of IAV, in preparation for the advent of future IAVs and pandemics.

Dataset Information

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

Publications

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

Similar Datasets

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