ArticleScience translational medicine2025
IFN-γ-resistant CD28 CAR T cells demonstrate increased survival, efficacy, and durability in multiple murine tumor models.
Article in Science translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- PTPN22 as a novel therapeutic target: a key intracellular checkpoint for NK cell therapy.Journal for immunotherapy of cancer · 2026Article
- RHOA Deletion Downregulates CD19 and Promotes Dysfunctional Immune Microenvironments in CAR-T Resistant Large B-cell Lymphomas.Blood cancer discovery · 2026Article
- Peripheral blood IFN-γ-producing T-cell subsets and soluble IL-2 receptor as independent prognostic biomarkers in NSCLC treated with immune checkpoint inhibitor-based therapy.Discover oncology · 2026Article
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- The Pleiotropic Roles of Cytokines in Chimeric Antigen Receptor T-cell Therapy.Cancer immunology research · 2026Review
- Fanning the flames: IFN-γ fuels CAR-T inflammation and cytopenia.The Journal of clinical investigation · 2026Article
- Adaptive immunotherapeutic paradigms in diffuse midline glioma: integrating epigenetic reprogramming, neuron-glioma interactions, and tumor microenvironment modulation.Journal of neuro-oncology · 2025Review
- Avoiding the toll of lung injury while driving CAR T cells to the target tumor.Journal of thoracic disease · 2025Article
- Engineering the tumor microenvironment: oncolytic NDV to facilitate CAR-T cell therapy.Journal of translational medicine · 2025Review
- Predictors of response to CD19 chimeric antigen receptor T-cell therapy in large B-cell lymphoma: a consolidated review.Current opinion in oncology · 2025Review
- Soil and Seed: Tumor Microenvironment Nurtures Immunotherapy Resistance and Renewal.International journal of molecular sciences · 2025Review
- Enhancing CAR-T cell efficacy through IFN ablation.Nature reviews. Drug discovery · 2025Article
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Authors and funding
22 authors.
Funding
Abstract
Interferon-γ (IFN-γ) plays complex and, sometimes, contradictory roles in cancer, which can affect patient responses to treatments such as immunotherapies. We recently demonstrated that IFN-γ production by chimeric antigen receptor (CAR) T cells is not required for efficacy in hematologic tumor models, whereas IFN-γ receptor (IFN-γR) signaling in solid tumor cells facilitates CAR T cell adhesion and antigen-specific cytotoxicity. Here, we show that IFN-γ induces apoptosis of CAR T cells bearing a CD28 intracellular signaling domain, which can be reduced through targeting of IFN-γ or IFN-γR. In hematologic malignancies, knockout of IFN-γR (IFN-γRKO) in CAR T cells increased their persistence without compromising efficacy. In xenograft and syngeneic solid tumor models, IFN-γR knockout CAR T cells displayed more potent tumor control, prolonged survival, and improved T cell memory that conferred protection from tumor rechallenge. RNA sequencing of tumor-infiltrating IFN-γRKO CAR T cells derived from tumor-bearing mice revealed increased cell death in tumor cells. Collectively, these data show that inhibition of IFN-γ signaling can increase the expansion and antitumor activity of CD28-based CAR T cells in liquid and solid tumors.
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