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• W2947142969 abstract "e14184 Background: Inflamed head and neck squamous cell carcinomas (HNSCC), have a better prognosis independently of the treatment modalities, and have an increased response rate to PD(L)1 blockade. Dendritic cells (DC) infiltration is associated to T cell infiltration and DC are critical in the immune response to cancer, but little is known on HNSCC infiltrating DC. The objectives were to determine the differences between DC infiltrating inflamed vs non inflamed tumors, to understand which mechanisms modulate DC phenotypes and which are the associated functions. Methods: 22 untreated HNSCC were characterized by flow cytometry for their immune infiltrate. RNA sequencing of sorted tumor infiltrating myeloid subsets and blood DC were analyzed for differentially expressed genes. The TMod database (Grandclaudon et al.), testing the effect of various stimuli on DC and subsequently on co-cultured T cells, was used to decipher DC and T cell modulation. Results: The level of CD3 infiltration was positively associated to the level of DC infiltration and PDL1 expression on myeloid cells, and negatively to the level neutrophils and of ICOSL expression on myeloid cells. PDL1high ICOSLneg DC from inflamed tumors were matched with the “innate DC” phenotype described in vitro, highly efficient at secreting cytokines and chemokines but poorly activating naïve CD4 T cells. DC from non-inflamed tumor resembled immature medium DC. A third type of DC, “adaptive DC”, expressing high levels of ICOSL and low of PDL1, poorly efficient at cytokine and chemokine secretion, but highly efficient at activating T cells is was described in vitro, but not found in tumors. RNAseq analysis confirmed this innate polarization and highlighted that those cells present a mature and NFkB activated phenotype. Conclusions: Inflamed HNSCC contain stimuli able to induce the recruitment and the differentiation of DC into mature, NFkB activated “innate” DC, highly efficient at secreting cytokines and chemokines but poorly activating naïve CD4 T cells. These data partly explain the superiority of CPS over TPS for the prediction of response to PD(L)1 blockade. More importantly, the stimuli identified here may be used as adjuvants to induce this DC « innate » maturation in non-inflamed tumors, but should only be used in combination with anti-PD(L)1 immunotherapy." @default.
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• W2947142969 date "2019-05-20" @default.
• W2947142969 modified "2023-10-15" @default.
• W2947142969 title "Use of PD-L1 and ICOSL to discriminate innate and adaptive dendritic cells in the head and neck cancer microenvironment." @default.
• W2947142969 doi "https://doi.org/10.1200/jco.2019.37.15_suppl.e14184" @default.
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