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- W4361818987 abstract "<div>AbstractPurpose:<p>Innate immunity is an indispensable arm of tumor immune surveillance, and the liver is an organ with a predominance of innate immunity, where mucosal-associated invariant T (MAIT) cells are enriched. However, little is known about the phenotype, functions, and immunomodulatory role of MAIT cells in hepatocellular carcinoma (HCC).</p><p><b>Experimental Design:</b> The distribution, phenotype, and function of MAIT cells in patients with HCC were evaluated by both flow cytometry (FCM) and <i>in vitro</i> bioassays. Transcriptomic analysis of MAIT cells was also performed. Prognostic significance of tumor-infiltrating MAIT cells was validated in four independent cohorts of patients with HCC.</p>Results:<p>Despite their fewer densities in HCC tumor than normal liver, MAIT cells were significantly enriched in the HCC microenvironment compared with other mucosa-associated organs. Tumor-derived MAIT cells displayed a typical CCR7<sup>−</sup>CD45RA<sup>−</sup>CD45RO<sup>+</sup>CD95<sup>+</sup> effector memory phenotype with lower costimulatory and effector capabilities. Tumor-educated MAIT cells significantly upregulated inhibitory molecules like PD-1, CTLA-4, TIM-3, secreted significantly less IFNγ and IL17, and produced minimal granzyme B and perforin while shifting to produce tumor-promoting cytokines like IL8. Transcriptome sequencing confirmed that tumor-derived MAIT cells were reprogrammed toward a tumor-promoting direction by downregulating genes enriched in pathways of cytokine secretion and cytolysis effector function like <i>NFKB1</i> and <i>STAT5B</i> and by upregulating genes like <i>IL8, CXCL12</i>, and <i>HAVCR2</i> (<i>TIM-3</i>). High infiltration of MAIT cells in HCC significantly correlated with an unfavorable clinical outcome, revealed by FCM, qRT-PCR, and multiplex IHC analyses, respectively.</p>Conclusions:<p>HCC-infiltrating MAIT cells were functionally impaired and even reprogrammed to shift away from antitumor immunity and toward a tumor-promoting direction.</p><p><i>See related commentary by Carbone, p. 3199</i></p></div>" @default.
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- W4361818987 date "2023-03-31" @default.
- W4361818987 modified "2023-09-22" @default.
- W4361818987 title "Data from Activated and Exhausted MAIT Cells Foster Disease Progression and Indicate Poor Outcome in Hepatocellular Carcinoma" @default.
- W4361818987 doi "https://doi.org/10.1158/1078-0432.c.6527418.v1" @default.
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