Regulatory T Cells in the Tumor Microenvironment and Cancer Progression: Role and Therapeutic Targeting

Abstract

Recent years have seen significant efforts in understanding and modulating the immune response in cancer. In this context, immunosuppressive cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), have come under intense investigation for their proposed roles in suppressing tumor-specific immune responses and establishing an immunosuppressive tumor microenvironment, thus enabling tumor immune evasion. Additionally, recent evidence indicates that Tregs comprise diverse and heterogeneous subsets; phenotypically and functionally distinct subsets of tumor-infiltrating Tregs could contribute differently to cancer prognosis and clinical outcomes. Understanding Treg biology in the setting of cancer, and specifically the tumor microenvironment, is important for designing effective cancer therapies. In this review, we critically examine the role of Tregs in the tumor microenvironment and in cancer progression focusing on human studies. We also discuss the impact of current therapeutic modalities on Treg biology and the therapeutic opportunities for targeting Tregs to enhance anti-tumor immune responses and clinical benefits.

Keywords: cancer progression; regulatory T cells; therapeutic targeting; tumor microenvironment; tumor-infiltrating lymphocytes.

Figure 1

Summary of currently approved and experimental therapies that may target Tregs; therapies are color-coded according to stage in clinical testing. Abbreviations—ADCC: antibody-dependent cell-mediated cytotoxicity, ADCP: antibody-dependent cellular phagocytosis, ATZB: atezolizumab, BV: bevacizumab, CTX: cyclophosphamide, DC: dendritic cell, DZB: daclizumab, CCR4: C-C motif chemokine receptor 4, DPT: diptheria toxin, FDB: fludarabine, IPB: ipilimumab, MGZ: mogamulizumab, NIVO: nivolumab, ONTAK: denileukin difitox, PTX: paclitaxel, SNB: sunitinib.