Tumor irradiation promotes antigen dressing of dendritic cells to enhance CAR T cell persistence and efficacy in lung metastases
Year: 2026
Type: article
Abstract: Metastatic solid tumors remain the principal cause of cancer mortality worldwide. High tumor burden impairs responses to chimeric antigen receptor (CAR) T cell therapy, yet off-tumor toxicity limits the doses that can be safely delivered. Strategies to selectively enhance CAR T cell activity at tumor sites could widen the therapeutic window. Using syngeneic models of extensive metastatic lung adenocarcinoma and melanoma, we show that 8 Gy of tumor irradiation significantly enhanced CAR T cell persistence in a manner critically dependent on dendritic cells (DCs). Irradiation promoted trogocytic antigen dressing of tumor antigens onto DCs, which then expanded CAR T cells through the chimeric receptor. Without functional DCs, irradiation failed to sustain CAR T cell persistence and tumors relapsed. Irradiation increased CAR T cell numbers within tumors but not in adjacent normal lung tissue that also expressed target antigen, conferring robust control of tumor without increased toxicity. These data define a mechanistic basis and rationale for combining radiotherapy with CAR T cell therapy.
Source: Nature Cancer
Authors: Sophia Navarre, Maki N. Ishibashi, Achuth Nair, Ivan Reyes-Torres, Meriem Belabed, Laszlo Halasz, Matthew D. Park, Raphaël Mattiuz, Merouane Ounadjela, Gertrude Gunset, Jorge Mansilla-Soto, Judith Feucht, Annalisa Cabriolu, Jessica Le Berichel, Alexander Birbrair, Justin Eyquem, Brian D. Brown, Miriam Merad, Michel Sadelain, Jalal Ahmed
Institutions: City College of New York, Icahn School of Medicine at Mount Sinai, University of Pittsburgh, Memorial Sloan Kettering Cancer Center, Columbia University Irving Medical Center, Moffitt Cancer Center, University Children's Hospital Tübingen, University of Tübingen, University of Wisconsin–Madison, University of California, San Francisco, Parker Institute for Cancer Immunotherapy
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: Conquer Cancer Foundation, American Society of Clinical Oncology, Lung Cancer Research Foundation, Regeneron Pharmaceuticals, Stanford Diabetes Research Center, Atara Biotherapeutics, National Institutes of Health, Genentech, Juno Therapeutics, NIH Office of the Director, National Cancer Institute
OpenAlex ID: W7162082285