The characterization of cutaneous squamous cell carcinoma (cSCC) at the molecular level is lacking in the current literature due to the high mutational burden of this disease. Immunosuppressed patients afflicted with cSCC experience considerable morbidity and mortality. In this article, we review the molecular profile of cSCC among the immunosuppressed and immunocompetent populations at the genetic, epigenetic, transcriptomic, and proteometabolomic levels, as well as describing key differences in the tumor immune microenvironment between these two populations. We feature novel biomarkers from the recent literature which may serve as potential targets for therapy.
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