Potent cytotoxic tumor infiltrating lymphocytes can be generated from immune-excluded chondrosarcomas using regulatable membrane-bound IL15
Tumor infiltrating lymphocyte (TIL) therapy shows promise against “hot” tumors but generation of potent TIL from cold tumors, such as many sarcoma types, is challenging, partly due to limited lymphocyte infiltration. Here, we report successful generation and expansion of TIL engineered with regulatable, membrane-bound IL15 from profoundly immune-excluded, paucicellular chondrosarcoma biopsies composed mainly of collagenous matrix and demonstrate potent tumor-killing without exogenous IL2. Importantly, IL15 reduced the signaling threshold of T-cell receptors isolated from TIL clonotypes, increasing their cytotoxicity. These results suggest the possibility of developing an effective IL2-free TIL therapy for patients with immune-excluded tumors.
This repository contains analysis code and data relevant to the manuscript.