Tumor irradiation promotes antigen dressing of dendritic cells to enhance CAR T cell persistence and efficacy in lung metastases
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.
Authors
- Judith Feucht (ORCID: https://orcid.org/0000-0002-8745-1079)
- Gertrude Gunset (ORCID: https://orcid.org/0009-0002-2715-6980)
- Justin Eyquem (ORCID: https://orcid.org/0000-0001-8262-1190)
- Alexander Birbrair (ORCID: https://orcid.org/0000-0003-1015-2561)
- Meriem Belabed (ORCID: https://orcid.org/0000-0002-3210-1581)
- Sammy Navarre
- Annalisa Cabriolu (ORCID: https://orcid.org/0000-0002-8216-2120)
- Merouane Ounadjela
- Michel Sadelain
- Jalal Ahmed (ORCID: https://orcid.org/0000-0002-1965-4069)
- Jorge Mansilla-Soto (ORCID: https://orcid.org/0000-0003-2889-1397)
- Jessica Le Berichel
- Raphaël Mattiuz (ORCID: https://orcid.org/0000-0002-3292-1635)
- Matthew D. Park
- Brian D. Brown (ORCID: https://orcid.org/0000-0002-3670-8778)
- Ivan Reyes-Torres
- Miriam Merad (ORCID: https://orcid.org/0000-0002-4481-7827)
- Maki N. Ishibashi
- Laszlo Halasz (ORCID: https://orcid.org/0000-0003-4726-7012)
- Achuth Nair
Institutions
- City College of New York (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of Wisconsin–Madison (US)
- University of Pittsburgh (US)
- Columbia University Irving Medical Center (US)
- Moffitt Cancer Center (US)
- Kettering University (US)
- Parker Institute for Cancer Immunotherapy (US)
- University Children's Hospital Tübingen (DE)
- Columbia University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Nature Cancer
- Published
- 2026-05-22
- DOI
- https://doi.org/10.1038/s43018-026-01167-6
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
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