Phenotypic alterations, clinical impact and therapeutic potential of regulatory T cells in cancer

Introduction: Regulatory T cells (Tregs) have been characterised in different cancers. They accumulate in peripheral blood and tumour microenvironments where they suppress tumour-specific immune responses, enabling tumours to develop without challenge. This tumour immune evasion represents a major obstacle to successful cancer therapies. Whilst Tregs are generally divided into thymic-derived and peripherally induced, Tregs exhibit a wide spectrum of phenotypes and functional capacity dependent on microenvironment. This phenotypic diversity is also reflected in tumour-infiltrating Treg (TI Treg) populations, which may explain the variable impact of Treg accumulation on prognosis in different cancers. Identifying TI Treg subsets is critical to understand TI Treg biology and for developing effective immunotherapies. Areas covered: This review discusses current and potential markers, and the modulation of these markers in cancer. In addition, we systematically review the clinical impact of Tregs in cancer and their potential as a therapeutic target, with a focus on TI Tregs. Expert opinion: TI Tregs represent dynamic and diverse subsets that are key in promoting tumour progression through their suppressive activities. Targeting specific TI Treg subpopulations and functional TI Treg markers represents a feasible therapeutic strategy that might allow reestablishment of antitumour immune responses without affecting physiological immune regulation.