Targeting T regulatory (Treg) cells in immunotherapy-resistant cancers

Spiliopoulou, P. , Kaur, P., Hammett, T., Di Conza, G. and Lahn, M. (2024) Targeting T regulatory (Treg) cells in immunotherapy-resistant cancers. Cancer Drug Resistance, 7, 2. (doi: 10.20517/cdr.2023.46) (PMID:38318526) (PMCID:PMC10838381)

Abstract

Primary or secondary (i.e., acquired) resistance is a common occurrence in cancer patients and is often associated with high numbers of T regulatory (Treg) cells (CD4+CD25+FOXP3+). The approval of ipilimumab and the development of similar pharmacological agents targeting cell surface proteins on Treg cells demonstrates that such intervention may overcome resistance in cancer patients. Hence, the clinical development and subsequent approval of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) targeting agents can serve as a prototype for similar agents. Such new agents aspire to be highly specific and have a reduced toxicity profile while increasing effector T cell function or effector T/T regulatory (Teff/Treg) ratio. While clinical development with large molecules has shown the greatest advancement, small molecule inhibitors that target immunomodulation are increasingly entering early clinical investigation. These new small molecule inhibitors often target specific intracellular signaling pathways [e.g., phosphoinositide-3-kinase delta (PI3K-δ)] that play an important role in regulating the function of Treg cells. This review will summarize the lessons currently applied to develop novel clinical agents that target Treg cells.

• Item Type: Articles
• Keywords: T regulatory cells, flow cytometry, primary and secondary resistance, mass cytometry, hyperprogression.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Spiliopoulou, Dr Pavlina
• Authors: Spiliopoulou, P., Kaur, P., Hammett, T., Di Conza, G., and Lahn, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cancer Drug Resistance
• Publisher: OAE Publishing
• ISSN: 2578-532X
• ISSN (Online): 2578-532X
• Copyright Holders: Copyright © 2024 The Authors
• First Published: First published in Cancer Drug Resistance 7:2
• Publisher Policy: Reproduced under a Creative Commons licence