ArticleCancer immunology, immunotherapy : CII2025
GPX4 is a key ferroptosis regulator orchestrating T cells and CAR-T-cells sensitivity to ferroptosis.
Article in Cancer immunology, immunotherapy : CII, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed.
- Ferroptosis in T cells: mechanisms, biology and translational opportunities.Nature reviews. Immunology · 2026Review
- Iron-mediated ferroptosis impairs CAR-T cell function and antitumor efficacy.Nature cancer · 2026Article
- Iron-ing out ferroptosis-mediated T cell dysfunction in cancer.Nature cancer · 2026Article
- GPX4 in the Tumor Microenvironment: Not Just Inhibiting Ferroptosis, but Immuno-Metabolic Regulation.Biomolecules · 2026Review
- Ferroptosis and chemotherapy resistance in ovarian cancer: molecular mechanisms and therapeutic opportunities.Journal of ovarian research · 2026Review
- Silicon-based agent alleviating intestinal ischemia/reperfusion injury in mice by inhibiting ferroptosis via activating AMPK-Sirt1 signaling pathway.Scientific reports · 2026Article
- Ferritinophagy as a Double-Edged Sword in Cancer: Novel Insights into Therapeutic Targeting of Iron-Driven Ferroptosis.Cell biochemistry and biophysics · 2026Review
- Selective disruption of lipid peroxide homeostasis in intratumoral regulatory T cells by targeting FSP1 enhances cancer immunity.Science advances · 2026Article
- Review
- Comprehensive pan-cancer analysis and experimental verification of the roles of SCP2 in colon adenocarcinoma.BMC cancer · 2026Article
- Programmed cell death in osteoarthritis.Apoptosis : an international journal on programmed cell death · 2026Review
- Succinylation in cancer immunotherapy: mechanisms, biomarkers, and therapeutic implications.Frontiers in immunology · 2026Review
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Research progress on ferroptosis in drug resistance and therapy of gastric cancer.Journal of cancer research and clinical oncology · 2025Review
- The dual nature of immunotherapy in female reproductive disorders: immune homeostasis and clinical challenges.Frontiers in immunology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors.
Funding
Abstract
Induction of ferroptosis, an iron-dependent form of regulated cell death, holds promise as a strategy to overcome tumor resistance to conventional therapies and enhance immunotherapy responses. However, while the susceptibility of tumor cells to ferroptosis is extensively studied, limited data exists on the vulnerability of immune cells to disturbed iron balance and lipid peroxidation. Here, we found that T-cell stimulation rewires iron and redox homeostasis and by increasing levels of reactive oxygen species and labile iron promotes lipid peroxidation and T-cells' ferroptosis. Upon stimulation, we detected changes in the balance of ferroptosis-suppressive proteins, including decrease of GPX4. Subsequently, we identified GPX4 as a master regulator orchestrating T/CAR-T-cells' sensitivity to ferroptosis and observed that GPX4 inhibitors impair CAR-T cells' antitumor functions. Our study demonstrated differential GPX4 expression and diverse susceptibility to ferroptosis between CD4⁺ and CD8⁺ T cells. Among analyzed subsets of naïve, central memory (CM), effector memory (EM), and terminally differentiated effector memory (TEMRA), CD8⁺ EM and CD8⁺ TEMRA cells exhibited the highest sensitivity to ferroptosis. We also showed that ferroptosis limited the anti-tumor efficacy of CAR-T cells, while ferroptosis inhibition improved their therapeutic effect, both in vitro and in vivo. Our findings are not only important to understand vulnerabilities of CAR-T cells but may also hold particular significance for their therapeutic development. In this context, future anticancer therapies should be carefully designed to selectively induce the ferroptosis of tumor cells without impeding cytotoxic cells' antitumor efficacy. Additionally, we postulate that promoting less differentiated phenotype of CAR-T cells should be exploited therapeutically to create CAR-T products characterized by decreased sensitivity to ferroptosis within tumor microenvironment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.