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    Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes by Kazuhiro Kakimi, Hirokazu Matsushita, Masaaki Komatsu, Eiryo Kawakami, Mikako Nishida, Nahoko Yamashita, Taisaku Ogawa, Keita Koseki, Eiji Warabi, Tomoyuki Ohue, Katsuyuki Shiroguchi, Heiichiro Udono

    Published 2021-09-01
    “…Melanoma cells containing an IFN-γ receptor (IFNγR) cytoplasmic domain deletion mutant was overexpressed and used for characterization of the metabolic profile of those tumor cells using a Seahorse Flux Analyzer.Results Met administration elevates mtROS and cell surface Glut-1, resulting in the production of IFN-γ in CD8TILs. mtROS activates Nrf2 in a glycolysis-dependent manner, inducing activation of autophagy, glutaminolysis, mTORC1, and p62/SQSTM1. mTORC1-dependent phosphorylation of p62 at serine 351 (p-p62(S351)) is also involved in activation of Nrf2. …”
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