IDO/TDO dual inhibitor

IL-6 levels decreased over the first three months for both intervention groups as well as the Control group (Supervised: p < 0.01, Home-based: p < 0.010, Control group: p < 0.01). Supervised resistance exercise might positively regulate the Kynurenine pathway and downregulate the kynurenine/tryptophan (indicative of IDO/TDO enzyme) levels, hence modulating the immune system.

To investigate the generalizability of our results, we also performed metabolomics and serum specimens from a large randomized Phase 3 trial (CheckMate 025) with 743 RCC patients, among which 394 received nivolumab and 349 received everolimus. We identified increased tryptophan to kynurenine conversion in response to PD1 blockade in a subset of melanoma and RCC patients. By using independent cohorts, we showed that Kyn/Trp temporal alterations robustly correlated with overall survival of patients receiving nivolumab. Our findings illustrate that checkpoint blockade in combination with IDO/TDO inhibitors might only benefit a selected group of patients with checkpoint-inhibition-triggered kynurenine pathway activation.

To investigate the generalizability of our results, we also performed metabolomics and serum specimens from a large randomized Phase 3 trial (CheckMate 025) with 743 RCC patients, among which 394 received nivolumab and 349 received everolimus. We identified increased tryptophan to kynurenine conversion in response to PD1 blockade in a subset of melanoma and RCC patients. By using independent cohorts, we showed that Kyn/Trp temporal alterations robustly correlated with overall survival of patients receiving nivolumab. Our findings illustrate that checkpoint blockade in combination with IDO/TDO inhibitors might only benefit a selected group of patients with checkpoint-inhibition-triggered kynurenine pathway activation.