PMC:6562565 / 64879-66099 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6562565","sourcedb":"PMC","sourceid":"6562565","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6562565","text":"The blockade of CTLA-4, an immune checkpoint receptor predominantly expressed by T cells and which competes with the co-stimulatory receptor CD28 for binding to CD80/CD86 on the surface of antigen presenting cells (APCs), has also generated durable clinical responses in advanced cancer patients (1). Tumor-bearing mice receiving CTLA-4 blockade and pharmacologic (389) or Ab-mediated (382) inhibition of CD73 display superior tumor control (382, 389) and overall survival (382) than counterparts receiving single agent treatments. Mechanistically, these dual therapies are more effective than corresponding monotherapies at increasing the intra-tumoral presence of tumor-specific CD8+ T cells (382), CD4+FoxP3neg T cells (389) as well as the levels of IFNγ (389) and of mRNA coding for IFNγ and T-bet (382). Likewise, concomitant provision of CTLA-4 ICB and antagonists of either A2AR (389) or A2BR (359) leads to decreased tumor growth (389) and metastasis formation (359), as well as to higher survival of tumor-bearing mice (359) when compared to single treatments. In terms of mechanisms, combining CTLA-4 ICB with an A2AR antagonist augments intratumoral CD8+ T cell presence as well as IFNγ and GzmB levels 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