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- W4362525097 abstract "<div>Abstract<p>Immunosuppression is common in head and neck squamous cell carcinoma (HNSCC). In previous studies, the TIGIT/CD155 pathway was identified as an immune-checkpoint signaling pathway that contributes to the “exhaustion” state of infiltrating T cells. Here, we sought to explore the clinical significance of TIGIT/CD155 signaling in HNSCC and identify the therapeutic effect of the TIGIT/CD155 pathway in a transgenic mouse model. TIGIT was overexpressed on tumor-infiltrating CD8<sup>+</sup> and CD4<sup>+</sup> T cells in both HNSCC patients and mouse models, and was correlated with immune-checkpoint molecules (PD-1, TIM-3, and LAG-3). TIGIT was also expressed on murine regulatory T cells (Treg) and correlated with immune suppression. Using a human HNSCC tissue microarray, we found that CD155 was expressed in tumor and tumor-infiltrating stromal cells, and also indicated poor overall survival. Multispectral IHC indicated that CD155 was coexpressed with CD11b or CD11c in tumor-infiltrating stromal cells. Anti-TIGIT treatment significantly delayed tumor growth in transgenic HNSCC mouse models and enhanced antitumor immune responses by activating CD8<sup>+</sup> T-cell effector function and reducing the population of Tregs. <i>In vitro</i> coculture studies showed that anti-TIGIT treatment significantly abrogated the immunosuppressive capacity of myeloid-derived suppressor cells (MDSC), by decreasing Arg1 transcripts, and Tregs, by reducing TGFβ1 secretion. <i>In vivo</i> depletion studies showed that the therapeutic efficacy by anti-TIGIT mainly relies on CD8<sup>+</sup> T cells and Tregs. Blocking PD-1/PD-L1 signaling increased the expression of TIGIT on Tregs. These results present a translatable method to improve antitumor immune responses by targeting TIGIT/CD155 signaling in HNSCC.</p></div>" @default.
- W4362525097 created "2023-04-06" @default.
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- W4362525097 date "2023-04-04" @default.
- W4362525097 modified "2023-09-27" @default.
- W4362525097 title "Data from Blockade of TIGIT/CD155 Signaling Reverses T-cell Exhaustion and Enhances Antitumor Capability in Head and Neck Squamous Cell Carcinoma" @default.
- W4362525097 doi "https://doi.org/10.1158/2326-6066.c.6550024" @default.
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