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In this study, we established a murine model of oral carcinogenesis using 4\u2010nitroquinoline\u20101\u2010oxide (4\u2010NQO) induction to investigate the impact of immunotherapy on microenvironmental alterations. Mice in the precancerous condition were randomly divided into two groups:\u00a0one receiving programmed death\u20101 (PD1) monoclonal antibody treatment and the other, control immunoglobulin G. Our observations showed that while PD1 blockade effectively delayed the progression of carcinogenesis, it did not completely impede or reverse it. To unravel the underlying reasons for the limited effectiveness of PD1 blockade, we collected tongue lesions and applied mass cytometry (CyTOF) and RNA sequencing (RNA\u2010seq) to characterize the microenvironment. CyTOF analysis revealed an increased macrophage subset (expressing high levels of IFN\u03b3 and iNOS) alongside a diminished Th1\u2010like subset (exhibiting low expression of TCF7) and three myeloid\u2010derived suppressor cell subsets (displaying low expression of MHC Class II or IFN\u03b3) following anti\u2010PD1 treatment. Notably, we observed an increased presence of cancer\u2010associated fibroblasts (CAFs) expressing collagen\u2010related genes after PD1 blockade. Furthermore, we found a negative correlation between the infiltration levels of CAFs and CD8<jats:sup>+<\/jats:sup> T cells. These findings were validated in murine tongue tissue slides, and publicly available multi\u2010omics datasets. Our results suggest that CAFs may impair the therapeutic efficacy of PD1 blockade in oral carcinogenesis by the remodeling of the extracellular matrix.<\/jats:p>","DOI":"10.1002\/mc.23670","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:28:39Z","timestamp":1702427319000},"page":"563-576","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mass cytometry and transcriptomic profiling reveal PD1 blockade induced alterations in oral carcinogenesis"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7252-3359","authenticated-orcid":false,"given":"Yunmei","family":"Dong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management Chinese Academy of Medical Sciences, West China Hospital of 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