Expression of costimulatory and inhibitory receptors in FoxP3+ regulatory T cells within the tumor microenvironment: Implications for combination immunotherapy approaches.

Expression of costimulatory and inhibitory receptors in FoxP3+ regulatory T cells within the tumor microenvironment: Implications for combination immunotherapy approaches. Adv Cancer Res. 2019;144:193-261 Authors: Toker A, Ohashi PS Abstract The unprecedented success of immune checkpoint inhibitors has given rise to a rapidly growing number of immuno-oncology agents undergoing preclinical and clinical development and an exponential increase in possible combinations. Defining a clear rationale for combinations by identifying synergies between immunomodulatory pathways has therefore become a high priority. Immunosuppressive regulatory T cells (Tregs) within the tumor microenvironment (TME) represent a major roadblock to endogenous and therapeutic tumor immunity. However, Tregs are also essential for the maintenance of immunological self-tolerance, and share many molecular pathways with conventional T cells including cytotoxic T cells, the primary mediators of tumor immunity. Hence the inability to specifically target and neutralize Tregs within the TME of cancer patients without globally compromising self-tolerance poses a significant challenge. Here we review recent advances in the characterization of tumor-infiltrating Tregs with a focus on costimulatory and inhibitory receptors. We discuss receptor expression patterns, their functional role in Treg biology and mechanistic insights gained from targeting these receptors in preclinical...
Source: Advances in Cancer Research - Category: Cancer & Oncology Authors: Tags: Adv Cancer Res Source Type: research