Research advances in the interplay between ferroptosis and T cells in the tumor microenvironment (Review)
- 1Key Laboratory of Oncology of Traditional Chinese Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, P.R. China
- 2Department of Traditional Chinese Medicine, Changsha Hospital for Maternal and Child Health Care, Changsha, Hunan 410007, P.R. China
Abstract
Despite advances in tumor immunotherapy, its clinical efficacy remains constrained by challenges such as limited response rates, drug resistance and an immunosuppressive microenvironment; moreover, conventional therapeutic strategies often overlook the key constraints imposed by intrinsic tumor cell death resistance and metabolic reprogramming on antitumor immune responses. Based on the aforementioned practical dilemmas, the present review focused on the reciprocal regulatory crosstalk between ferroptosis and T cell immunity within the tumor microenvironment (TME) and further proposes novel therapeutic strategies that co-target ferroptosis in tumor cells and T cell immunity. Ferroptosis substantially strengthens T cell-dependent antitumor immunity. In turn, activated T cells dynamically regulate the susceptibility of tumor cells to ferroptosis, forming a positive immune feedback loop. Related combinatorial strategies have shown synergistic potential in preclinical studies, opening promising avenues to overcome existing therapeutic resistance. Nevertheless, multiple barriers impede clinical translation, including tumor heterogeneity, off-target toxicity of ferroptosis inducers and dysregulation of T cell subset balance. To address these issues, future application of nanodelivery systems for TME-specific intervention, combined with differential metabolic remodeling to reshape immunosuppressive networks, is expected to drive the development of next-generation precision immunotherapeutic combinations. Collectively, the present review systematically elucidated the mechanistic interplay between ferroptosis and T cell immunometabolism, providing a theoretical foundation for developing targeted therapies to overcome tumor immune resistance.
Related
- Mitophagy and Ferroptosis in Diabetic Kidney Disease: A Hypothesis of Their Synergistic Interplay in Renal Tubular Injury—A Narrative Review
- Clinical research advances in pulmonary infections in 2025: a narrative review of multipathogen assessment, precision diagnosis, and integrated management
- A review of advances in research on mechanisms inhibiting kidney stone formation from a network pharmacology perspective
- Ferroptosis in Intervertebral Disc Degeneration: How the Extreme Microenvironment Rewires a Cell Death Network
- Advances in Research on the Genotype–Phenotype Correspondence of Antibiotic Resistance in Helicobacter pylori and Its Molecular Mechanisms: A Narrative Review
BibTeX
@article{tang2026research,
title = {{Research advances in the interplay between ferroptosis and T cells in the tumor microenvironment (Review)}},
author = {Shihan Tang and Wenbo Xu and Yichen Li and Chuwei Liu and Weitao Liu and Ruihan Liang and Qianhui Liao and Han Sun and Zhuoyan Wang and Lingchang Shi and Qiying Liu and Huiping Liu},
journal = {Molecular Medicine Reports},
year = {2026},
month = oct,
doi = {10.3892/mmr.2026.14048},
url = {https://doi.org/10.3892/mmr.2026.14048},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Research advances in the interplay between ferroptosis and T cells in the tumor microenvironment (Review)
AU - Shihan Tang
AU - Wenbo Xu
AU - Yichen Li
AU - Chuwei Liu
AU - Weitao Liu
AU - Ruihan Liang
AU - Qianhui Liao
AU - Han Sun
AU - Zhuoyan Wang
AU - Lingchang Shi
AU - Qiying Liu
AU - Huiping Liu
PY - 2026
DA - 2026/10/21
JO - Molecular Medicine Reports
DO - 10.3892/mmr.2026.14048
UR - https://doi.org/10.3892/mmr.2026.14048
AB - Despite advances in tumor immunotherapy, its clinical efficacy remains constrained by challenges such as limited response rates, drug resistance and an immunosuppressive microenvironment; moreover, conventional therapeutic strategies often overlook the key constraints imposed by intrinsic tumor cell death resistance and metabolic reprogramming on antitumor immune responses. Based on the aforementioned practical dilemmas, the present review focused on the reciprocal regulatory crosstalk between ferroptosis and T cell immunity within the tumor microenvironment (TME) and further proposes novel therapeutic strategies that co-target ferroptosis in tumor cells and T cell immunity. Ferroptosis substantially strengthens T cell-dependent antitumor immunity. In turn, activated T cells dynamically regulate the susceptibility of tumor cells to ferroptosis, forming a positive immune feedback loop. Related combinatorial strategies have shown synergistic potential in preclinical studies, opening promising avenues to overcome existing therapeutic resistance. Nevertheless, multiple barriers impede clinical translation, including tumor heterogeneity, off-target toxicity of ferroptosis inducers and dysregulation of T cell subset balance. To address these issues, future application of nanodelivery systems for TME-specific intervention, combined with differential metabolic remodeling to reshape immunosuppressive networks, is expected to drive the development of next-generation precision immunotherapeutic combinations. Collectively, the present review systematically elucidated the mechanistic interplay between ferroptosis and T cell immunometabolism, providing a theoretical foundation for developing targeted therapies to overcome tumor immune resistance.
SN - 1791-2997
SN - 1791-3004
ER -