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World J Clin Oncol. Oct 24, 2025; 16(10): 110466
Published online Oct 24, 2025. doi: 10.5306/wjco.v16.i10.110466
Expansion strategies for Vδ2 γδT cells in cancer immunotherapy: Activation, cytokines, and culture conditions
Natalia Lehman, Michal Zarobkiewicz
Natalia Lehman, Michal Zarobkiewicz, Department of Clinical Immunology, Medical University of Lublin, Lublin 20-093, Lubelskie, Poland
Natalia Lehman, Department of Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, Lublin 20-090, Lubelskie, Poland
Author contributions: Lehman N contributed to writing, and was responsible for figure and table preparation; Zarobkiewicz M conceived the idea, led the writing of the manuscript, and supervised the overall work; all authors contributed to revisions and approved the final version of the manuscript.
Supported by National Science Center of Poland, No. 2019/35/N/NZ6/02973.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Michal Zarobkiewicz, MD, PhD, Associate Professor, Department of Clinical Immunology, Medical University of Lublin, Chodzki 4A, Lublin 20-093, Lubelskie, Poland. michal.zarobkiewicz@umlub.pl
Received: June 9, 2025
Revised: July 3, 2025
Accepted: September 23, 2025
Published online: October 24, 2025
Processing time: 139 Days and 20.3 Hours
Abstract

The γδT cells are an emerging class of immune effectors with potent antitumor activity, bridging innate and adaptive immunity. Their unique ability to recognise stress-induced ligands independently of major histocompatibility complex restriction makes them attractive candidates for cancer immunotherapy. However, the clinical application of γδT cells requires efficient in vitro expansion strategies to generate large numbers of functional cells. This mini-review explores the latest advancements in γδT cell expansion protocols, focusing on key activation stimuli, cytokine support, and culture conditions that optimise proliferation and cytotoxicity.

Keywords: Vδ2; γδT; Expansion; Immunotherapy; Zoledronate; N-aminobisphosphonates; Mevalonate pathway

Core Tip: Vδ2 γδT cells hold promise for cancer immunotherapy due to their major histocompatibility complex-independent recognition of phosphoantigens and relative ease of their large scale GMP-compliant expansion in vitro. This mini-review outlines current strategies to optimize Vδ2 T cell expansion, highlighting the roles of stimuli, cytokine combinations, and culture conditions. Emerging insights on direct phosphoantigen stimulation and Toll-like receptor-based co-stimulation are also discussed, offering new avenues to enhance γδT cell yield and functionality for therapeutic use.