ArticleNature cancer2025
CAR-engineered lymphocyte persistence is governed by a FAS ligand-FAS autoregulatory circuit.
Article in Nature cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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.
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Who cites it
31 citing papers in PubMed.
- Targeted delivery of mRNA to immune cells forDrug delivery · 2026Review
- Depletion of an immature cord blood NK subset reverses trogocytosis-driven CAR NK dysfunction.Cancer cell · 2026Article
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- Fas acts as a T cell co-stimulatory receptor via both death domain-independent and -dependent mechanisms.Cell death and differentiation · 2026Article
- Class I HDAC inhibition enhances the stem-like memory properties of CRISPR-engineered CAR T cells in neuroblastoma.Molecular therapy. Oncology · 2026Article
- HLA micropolymorphisms confine neoantigen conformational adaptability and guide T cell receptor selectivity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Design principles of the cytotoxic CD8Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Engineering CAR-Vδ2 T cells to boost persistence and anti-tumor function.bioRxiv : the preprint server for biology · 2026Article
- A PI3Kδ-Foxo1-FasL signaling amplification loop rewires CD4+ T cell signaling and differentiation.The Journal of experimental medicine · 2026Article
- Co-editing of NKG2A and FAS increases long-term cytotoxic capacity and persistence of CAR NK cells.Molecular therapy. Oncology · 2026Article
- Ibrutinib and PD-1 Blockade Potentiate Mesothelin-Targeting CAR T-cell Therapy in Preclinical Models of Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Iparomlimab and tuvonralimab (QL1706) combined definitive chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma (QL1706-IIT-02): a single arm, phase 2 trial.EClinicalMedicine · 2026Article
- The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.Frontiers in immunology · 2026Review
- Enhancing CAR-NK persistence to unlock its full therapeutic potentials.Frontiers in immunology · 2026Review
- A new era in CAR-NK cell therapy: from technological innovations to clinical applications.World journal of pediatrics : WJP · 2026Review
- Emerging Chimeric Antigen Receptor-Immune Cell Therapy for Pancreatic Cancer: Mechanisms, Clinical Advances, and Future Perspectives.Oncology research · 2026Review
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23 authors.
Funding
Abstract
Chimeric antigen receptor (CAR)-engineered lymphocytes treat B cell malignancies; however, limited persistence can restrain the full therapeutic potential of this approach. FAS ligand (FAS-L)/FAS interactions govern lymphocyte homeostasis. Knowledge of which cells express FAS-L in patients with cancer and whether these sources compromise CAR persistence remains incomplete. Here, we constructed a single-cell atlas of diverse cancers to identify cellular subsets expressing FASLG, the gene encoding FAS-L. We discovered that FASLG expression is limited primarily to endogenous T cells, natural killer (NK) cells and CAR-T cells, while tumor and stromal cell expression is minimal. To establish whether CAR-T and CAR-NK cell survival is FAS-L regulated, we performed competitive fitness assays using FAS-dominant negative receptor (ΔFAS)-modified lymphocytes. Following transfer, ΔFAS-expressing CAR-T/CAR-NK cells became enriched, a phenomenon that mechanistically was reverted through FASLG knockout. By contrast, FASLG was dispensable for CAR-mediated tumor killing. In multiple models in female mice, ΔFAS coexpression enhanced antitumor efficacy. Together, these findings reveal that CAR-engineered lymphocyte persistence is governed by a FAS-L/FAS autoregulatory circuit.
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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.