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Review
. 2019 Jul;157(3):198-209.
doi: 10.1111/imm.13058. Epub 2019 Apr 29.

Treg programming and therapeutic reprogramming in cancer

Mariela A Moreno Ayala  1 , Zehui Li  1 , Michel DuPage  1
Affiliations
Review

Treg programming and therapeutic reprogramming in cancer

Mariela A Moreno Ayala et al. Immunology. 2019 Jul.

Abstract

Overcoming the immunosuppressive tumour microenvironment is the major challenge impeding cancer immunotherapy today. Regulatory T-cells (Tregs) are prevalent in nearly all cancers and, as immunosuppressive regulators of immune responses, they are the principal opponents of cancer immunotherapy. However, disabling Tregs systemically causes severe autoimmune toxicity, hastening the need for more selective methods to target intratumoural Tregs. In this review, we discuss a burgeoning new modality to specifically target tumour-infiltrating Tregs (TI-Tregs) by reprogramming their functionality from immunosuppressive to immune stimulatory within tumours. As the basis for therapeutic selectivity of TI-Tregs, we will focus on the defining features of Tregs within cancer: their highly activated state controlled by the engagement of key surface receptors, their distinct metabolic programme, and their unique transcriptional programme. By identifying proteins and pathways that distinguish TI-Tregs from other Tregs in the body, as well as from the beneficial antitumour effector T-cells within tumours, we highlight mechanisms to selectively reprogramme TI-Tregs for the treatment of cancer.

Keywords: Treg; cancer; tumour immunology.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Signals and pathways critical for the stability of tumour‐infiltrating regulatory T‐cells (TI‐Tregs). Here we demarcate five interconnected nodes (receptors, cytosolic signalling, metabolism, transcription factors and chromatin regulation) that together programme Treg immunosuppression. Reprogramming of TI‐Tregs from immunosuppressive to immune stimulatory activities is achieved by the disruption of these critical pathways (see highlighted lines and arrows in the figure).
See this image and copyright information in PMC

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