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Cellular heterogeneity in OSCC\u2010GB was investigated by single\u2010cell RNA sequencing of tumors derived from the oral cavity of 12 OSCC\u2010GB patients, 3 of whom had concomitant presence of a precancerous lesion (oral submucous fibrosis [OSMF]). Unique malignant cell types, features, and phenotypic shifts in the stromal cell population were identified in oral tumors with associated submucous fibrosis. Expression levels of <jats:italic>FOS<\/jats:italic>, <jats:italic>ATP1A<\/jats:italic>, and <jats:italic>DUSP1<\/jats:italic> provided robust discrimination between tumors with or without the concomitant presence of OSMF. Malignant cell populations shared between tumors with and without OSMF were enriched with the expression of partial epithelial\u2013mesenchymal transition (pEMT) or fetal cell type signatures indicative of two dominant cellular programs in OSCC\u2010GB\u2014pEMT and fetal cellular reprogramming. Malignant cells exhibiting fetal cellular and pEMT programs were enriched with the expression of immune\u2010related pathway genes known to be involved in antitumor immune response. In the tumor microenvironment, higher infiltration of immune cells than the stromal cells was observed. The T cell population was large in tumors and diverse subtypes of T cells with varying levels of infiltration were found. We also detected double\u2010negative <jats:italic>PLCG2<\/jats:italic><jats:sup>+<\/jats:sup> T cells and cells with intermediate M1\u2013M2 macrophage polarization. Our findings shed light on unique aspects of cellular heterogeneity and cell states in OSCC\u2010GB.<\/jats:p>","DOI":"10.1111\/cas.15979","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T16:50:25Z","timestamp":1696438225000},"page":"4732-4746","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Single\u2010cell transcriptomic analysis of gingivo\u2010buccal oral cancer reveals two dominant cellular programs"],"prefix":"10.1111","volume":"114","author":[{"given":"Sillarine","family":"Kurkalang","sequence":"first","affiliation":[{"name":"National Institute of Biomedical Genomics  Kalyani India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumitava","family":"Roy","sequence":"additional","affiliation":[{"name":"National Institute of Biomedical Genomics  Kalyani India"},{"name":"Regional Centre for Biotechnology  Faridabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunima","family":"Acharya","sequence":"additional","affiliation":[{"name":"National Institute of Biomedical Genomics  Kalyani India"},{"name":"Regional Centre for Biotechnology  Faridabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paramita","family":"Mazumder","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology Dr. R. 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