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• W2988788707 abstract "Cancers of the oral cavity remain the sixth most diagnosed cancer worldwide, with high rates of recurrence and mortality. We determined the role of STAT1 during oral carcinogenesis using two orthotopic models in mice genetically deficient for Stat1 . Metastatic (LY2) and nonmetastatic (B4B8) head and neck squamous cell carcinoma (HNSCC) cell lines were injected into the oral cavity of Stat1 deficient ( Stat1 −/− ) and Stat1 competent ( Stat1 +/+ ) mice. Stat1 −/− mice displayed increased tumor growth and metastasis compared to Stat1 +/+ mice. Mechanistically, Stat1 −/− mice displayed impaired CD4+ and CD8+ T‐cell expansion compared to Stat1 +/+ mice. This was associated with enhanced T‐cell exhaustion, and severely attenuated T‐cell antitumor effector responses including reduced expression of IFN‐γ and perforin at the tumor site. Interestingly, tumor necrosis factor (TNF)‐α production by T cells in tumor‐bearing mice was suppressed by Stat1 deficiency. This deficiency in T‐cell expansion and functional responses in mice was linked to PD‐1 and CD69 overexpression in T cells of Stat1 −/− mice. In contrast, we observed increased accumulation of CD11b+ Ly6G+ myeloid derived suppressor cells in tumors, draining lymph nodes, spleens and bone marrow of tumor‐bearing Stat1 −/− mice, resulting in a protumorigenic microenvironment. Our data demonstrates that STAT1 is an essential mediator of the antitumor response through inhibition of myeloid derived suppressor cell accumulation and promotion of T‐cell mediated immune responses in murine head and neck squamous cell carcinoma. Selective induction of STAT1 phosphorylation in HNSCC patients could potentially improve oral tumor outcomes and response to therapy." @default.
• W2988788707 created "2019-11-22" @default.
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• W2988788707 date "2019-11-29" @default.
• W2988788707 modified "2023-09-30" @default.
• W2988788707 title "STAT1 inhibits T‐cell exhaustion and myeloid derived suppressor cell accumulation to promote antitumor immune responses in head and neck squamous cell carcinoma" @default.
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• W2988788707 doi "https://doi.org/10.1002/ijc.32781" @default.
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• W2988788707 hasPublicationYear "2019" @default.
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