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Theses/Dissertations

2016

Metabolism

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Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer Jan 2016

Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer

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Overcoming cancer cell immune escape represents a fundamental obstacle in the treatment of cancer. Indoleamine 2,3-dioxygenase (IDO)-expressing myeloid-derived suppressor cells (MDSCs) are known to induce oxidative stress and alter amino acid metabolism within the tumor microenvironment (TME). The tryptophan (Trp)-catabolizing action of IDO not only promotes T cell tolerance and evasion but is also associated with impaired quality of life in cancer patients. We have previously demonstrated that a novel combination therapy, consisting of MDSC-depleting gemcitabine and a superoxide dismutase mimetic, prolonged survival of tumor-bearing mice by enhancing CD8+ memory T cell metabolism. We identify that combination therapy inhibits IDO …