The Role of Regulatory T Cells in Cancer Treatment Resistance

Int J Mol Sci. 2023 Sep 14;24(18):14114. doi: 10.3390/ijms241814114.

Abstract

Despite tremendous progress in cancer treatment in recent years, treatment resistance is still a major challenge for a great number of patients. One of the main causes is regulatory T lymphocytes (Tregs), which suppress excessive inflammatory responses via the secretion of immunosuppressive cytokines and upregulate the immune checkpoints. Their abundance causes an immunosuppressive reprogramming of the tumor environment, which is ideal for tumor growth and drug inefficiency. Hence, regiments that can regain tumor immunogenicity are a promising strategy to overcome Tregs-mediated drug resistance. However, to develop effective therapeutic regimens, it is essential to understand the molecular mechanisms of Treg-mediated resistance. In this article, we gathered a comprehensive summary of the current knowledge on molecular mechanisms and the role of Tregs in cancer treatment resistance, including cancer immunotherapy, targeted therapy, chemotherapy, and radiotherapy.

Keywords: chemotherapy; immunotherapy; radiotherapy; regulatory T cell; resistance mechanisms.

Publication types

  • Review

MeSH terms

  • Cytokines
  • Humans
  • Immunosuppressive Agents
  • Immunotherapy
  • Neoplasms* / therapy
  • Radiation Oncology*
  • T-Lymphocytes, Regulatory

Substances

  • Cytokines
  • Immunosuppressive Agents

Grants and funding

This research was supported by the Foundation for Polish Science under the International Research Agendas Program financed from the Smart Growth Operational Program 2014–2020 (Grant Agreement No. MAB/2018/6). At the time of manuscript preparation A.P. was supported with Walczak’s Scholarship funded by NAWA-Polish National Agency for Academic Exchange (Scholarship Agreement No. BPN/WAL/2022/1/00024/U/00001).