Immunometabolic modulation by targeting UCP2 and IL-17A boost anti-tumor immunity against pancreatic cancer

Abstract Metabolic reprograming of cytotoxic effectors by tumor microenvironment (TME) is one the key mechanisms which TME impairs success cancer immunotherapy. Therapeutic strategies that mitigate immunosuppressive and selectively enhance bioenergetic fitness may benefits immunotherapy, particularly in TME-abundant pancreatic cancer. IL-17 a cytokine engaged feed-forward loop promoting milieu facilitates progression. Mitochondrial uncoupling protein 2 (UCP2) acts as an inhibitor T cell metabolic directly promotes tumorigenesis. Therefore, we hypothesized targeting UCP2 could act additionally to antitumor immune response inhibit growth. deficiency regulated metabolism mTOR signaling cells IFN-γ production anti-tumor responses. inhibition increased immunity PBMCs tumors patients with PDAC. The dual boosted suppressed tumorigenesis tumor-bearing mice. Combination blockade offer additional complimentary cooperative against 1. Ministry Science Technology (MOST 108-2320-B-039-024-MY3) 2. China Medical University Hospital (DMR-110-186) 3. Chinese Medicine Research Center, from Featured Areas 4. Center Program within framework Higher Education Sprout Project (CMRC-CHM-2)