2026-06-01 マウントサイナイ医療システム（MSHS）
CAR-T cells (brown, arrowheads) infiltrating solid tumors. Left: unirradiated (0 Gy). Right: after focal irradiation (8 Gy).
＜関連情報＞
- https://www.mountsinai.org/about/newsroom/2026/irradiation-may-help-car-t-cell-therapy-work-better-against-solid-tumors-mount-sinai-researchers-find
- https://www.nature.com/articles/s43018-026-01167-6
腫瘍への放射線照射は、樹状細胞の抗原ドレッシングを促進し、肺転移におけるCAR T細胞の持続性と有効性を高める Tumor irradiation promotes antigen dressing of dendritic cells to enhance CAR T cell persistence and efficacy in lung metastases
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
Nature Cancer Published:22 May 2026
DOI:https://doi.org/10.1038/s43018-026-01167-6
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.
