Robust T cell activation kills tumors regardless of T cell specificity

Here, we show how T cells can eliminate tumors without tumor-specificity via paracrine signaling. Activating unexhausted bystander non-tumor-specific T cells within tumors resulted in tumor elimination without conventional recognition-dependent mechanisms and in the absence of any tumor-specific TCRαâ T cell.

Robust T cell activation recruited immune cells, utilized innate leukocytes, and triggered a tumoricidal combination of effector molecules and panoptotic pathways. Mechanistically, IFN-γ, TNF, and NO induced caspase-dependent death, recapitulating melanoma clearance in mice or human melanoma cell death in vitro. Gene expression signatures associated with this response in mice predicted survival among human melanoma patients.