Regulatory T cells in cancer: where are we now?

Abstract

Summary There have been substantial strides forward in our understanding of the contribution of regulatory T (Treg) cells to cancer immunosuppression. In this issue, we present a series of papers highlighting emerging themes on this topic relevant not only to our understanding of the fundamental biology of tumour immunosuppression but also to the design of new immunotherapeutic approaches. The substantially shared biology of CD4+ conventional T (Tconv) and Treg cells necessitates a detailed understanding of the potentially opposing functional consequences that immunotherapies will have on Treg and Tconv cells, a prominent example being the potential for Treg‐mediated hyperprogressive disease following anti‐PD‐1 therapy. Such understanding will aid patient stratification and the rational design of combination therapies. It is also becoming clear, however, that Treg cells within tumours exhibit distinct biological features to both Tconv cells and Treg cells in other tissues. These distinct features provide the opportunity for development of targeted immunotherapies with greater efficacy and reduced potential for inducing systemic toxicity.

Blocking inflammation to improve immunotherapy of advanced cancer

“…High concentrations of ROS induce also specific alterations in TCR signaling, including conformational changes of TCR‐ζ and the tyrosine kinase LCK, thereby reducing phosphorylation and calcium flux, with consequent suppression of antigen‐mediated Tconv cell responses . The difficulty of remodeling lymphocytes with these functional defects could explain the failure of immunotherapy noted by Gallimore et al …”

“…The crucial contribution of regulatory T (Treg) cells to cancer immunosuppression, and their role in immunotherapy, has been extensively reviewed …”

“…In a recent review series in Immunology , Gallimore et al . indicated that the induction of selective recruitment and modulation of different Treg cell molecular profiles and functions in the tumor microenvironment was an extremely important therapeutic opportunity.…”

“…However, Gallimore et al . in their Editorial also highlighted the inadequate clinical responses to immunotherapies observed in poorly defined subsets of patients, and hence the need to provide a basis for patient stratification that is useful for identifying effective combination immunotherapy protocols.…”

“…The crucial contribution of regulatory T (Treg) cells to cancer immunosuppression, and their role in immunotherapy, has been extensively reviewed. 1 Treg cells represent a T-cell lineage assigned to suppressive activities and characterized by the expression of the transcription factor Foxp3. Foxp3 is crucial in stabilizing the Treg cells by inducing a gene expression profile specific for their suppressive functions.…”