A metabolic reprogramming strategy revitalises terminally exhausted T-cells and enhances the response to cancer immunotherapy

Research led by Ping-Chih Ho of the Ludwig Lausanne branch, in collaboration with Li Tang (EPFL), set about addressing how to restore the proliferative capacity of exhausted CD8+ tumour infiltrating lymphocytes (TILs), a key TILs subset when it comes to eliciting response to immunotherapy treatment.

The fixed exhausted state in tumor-reactive T cells represents a major bottleneck for harnessing host anti-tumor immunity and inducing responsiveness to anti-PD-1 treatment. Findings of this research point to IL-10’s capacity to reinvigorate both anti-tumor functions and proliferative capacity, via a specialised metabolic reprogramming. The published results of the application of this strategy in pre-clinical models establish robust anti-tumor immunity with CAR T-cell and PD-1 blockade immunotherapy.

This work was supported by the ISREC Foundation, University of Lausanne, Ludwig Institute for Cancer Research and the ERC.