Regulatory T cell targeting in cancer: Emerging strategies in immunotherapy

Abstract

The adaptive immune system is modulated by an important subset of CD4+ T lymphocytes called Treg cells that function in maintaining immune homeostasis by preventing excessive immune activation. Both deficiency and overactivation of Treg cell function can result in disease pathology. While loss of Treg function can lead to autoimmunity, an overabundance of Treg activity can promote tumorigenesis. Blocking and/or depleting Tregs has emerged as a viable strategy to enhance antitumor immunity. A major limitation underlying the limited efficacy observed with Treg therapies in the clinic is lack of selective targeting, often attributed to concurrent depletion of antitumor effector T‐cell populations. Novel approaches to improve the specificity of Treg targeting in the context of cancer include the use of T‐cell receptor mimic antibodies, bispecific antibodies, and near‐infrared photoimmunotherapy. Next‐generation technology platforms and transcriptomic/computational‐based screening methods have been recently developed to identify preferential Treg targets. Herein, we highlight key advancements and challenges pertaining to the development of novel Treg targeting cancer therapeutics and discuss ongoing clinical trials evaluating next‐generation Treg therapies for solid tumors.

Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy.

“… 17 A number of approaches are being tested to improve selectivity of immune-based interventions towards T-reg depletion or functional modulation: our result provide a rational basis for their development in combination with TACE. 48 …”

Regulatory T Cell Therapy of Graft-versus-Host Disease: Advances and Challenges

“…Several start-up companies have recently been funded with the aim of applying genetically engineered Tregs to treat autoimmune and alloimmune conditions [ 232 ]. The first CAR-Treg clinical trial has been granted authorization in the UK and the Netherlands (STEADFAST) applying anti-HLA-A2 CD4 Tregs in kidney transplant patients (EUCTR2019-001730-34-NL).…”

Metabolites in the Tumor Microenvironment Reprogram Functions of Immune Effector Cells Through Epigenetic Modifications

“…Till now, the overview landscape for tumor infiltrated immune cells has been largely established and can be briefly classified into two functional populations, immune suppressive and effector cell. The typical infiltrated suppressive cell includes regulatory T/B cell (T reg /B reg ), myeloid-derived suppressor cell (MDSC), M2like Macrophage, etc., which had been reviewed previously (13)(14)(15)(16). As for as infiltrated immune effector cell is concerned, CD8 + cytotoxic T cell, Th1, NK, and gd T cell are representative populations and have been extensively investigated.…”