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• W4220682261 endingPage "92" @default.
• W4220682261 startingPage "85" @default.
• W4220682261 abstract "Hypoxia is common in solid tumors and creates an immunosuppressive environment that leads to resistance to immunotherapy, such as an anti-programmed death receptor-1 (PD-1) therapy. It has been suggested that anti-PD-1 therapy may reduce tumor hypoxia by remodeling the tumor vasculature; however, it is unclear how anti-PD-1 therapy reduces hypoxia over time. Therefore, we investigated the relationship between hypoxia and immune activation by anti-PD-1 therapy in murine cancer models.Anti-PD-1 antibody was injected to CT26- and MC38-tumor-bearing mice on days 0 and 5. Tumor hypoxia was non-invasively evaluated using positron emission tomography (PET) with [18F]fluoromisonidazole ([18F]FMISO) on days 3 and 7. Histological analysis was conducted to investigate the infiltration of immune cells in [18F]FMISO-accumulated hypoxic area. In addition, the immune cell population in tumors and the percentages of cancer and immune cells under hypoxic conditions were analyzed at single-cell level using flow cytometry.Flow cytometric analysis of CT26 tumors on day 3 showed that anti-PD-1 therapy reduced hypoxia without inhibition of tumor growth. In addition, the infiltration of CD8+ T cells was increased in treated tumors. In contrast to CT26 tumors, the percentage of hypoxic cells in MC38 tumors did not change on days 3 and 7, and there was minimal immune activation induced by anti-PD-1 antibody. Changes in hypoxia in CT26 tumors were not detected by [18F]FMISO-PET, but autoradiogram showed that [18F]FMISO accumulated in immunosuppressed areas, where the infiltration of immune cells was relatively low.Reduction of hypoxia was induced in CT26 tumor, in which adequate immune response to anti-PD-1 therapy was exhibited, at an early time point before suppression of tumor growth. Our findings suggest that anti-PD-1 therapy can create a tumor microenvironment that facilitates immune activation by reducing hypoxia." @default.
• W4220682261 created "2022-04-03" @default.
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• W4220682261 date "2022-05-01" @default.
• W4220682261 modified "2023-10-14" @default.
• W4220682261 title "Reduction of tumor hypoxia by anti-PD-1 therapy assessed using pimonidazole and [18F]FMISO" @default.
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• W4220682261 doi "https://doi.org/10.1016/j.nucmedbio.2022.03.005" @default.
• W4220682261 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35367730" @default.
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