Lymphoma response to chimeric antigen receptor T cell therapy is driven by endogenous tumor-reactive CD8⁺ T cells

Durable CD19 CAR-T efficacy in relapsed or refractory large B-cell lymphoma is driven by cooperation with endogenous CD8 T cells, with CD8 depletion leading to relapse in mice.

• Why it matters: Most patients with large B-cell lymphoma fail to respond or relapse after CAR-T, and the mechanisms determining durable remission are unclear.
• What they did: Whole-genome and transcriptome profiling of 54 patients plus functional assays, syngeneic models, and mathematical modeling tested whether endogenous CD8 T cells are required for sustained responses.
• The result: In mice, sustained responses occurred only with endogenous CD8 cells, while all CD8-depleted mice relapsed after initial regression; patients and murine ELISPOT assays showed enhanced endogenous T-cell activation post-CAR-T.