Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer, with its incidence rising steeply. Immunosuppression is a well-established risk factor for cSCC, and this risk factor highlights the critical role of the immune system in regulating cSCC development and progression. Further highlighting the nature of cSCC as an immunological disorder, substantial evidence demonstrates a tight association between cSCC risk and age-related immunosenescence. Besides the proven efficacy of immune checkpoint blockade therapy for advanced cSCC, novel immunotherapy that targets cSCC precursor lesions has shown efficacy for cSCC prevention. Furthermore, the appreciation of the interplay between keratinocytes, commensal papillomaviruses, and the immune system has revealed the possibility for the development of a preventive cSCC vaccine. cSCC shares fundamental aspects of its origin and pathogenesis with mucosal SCCs. Therefore, advances in the field of cSCC immunoprevention will inform our approach to the management of mucosal SCCs and potentially other epithelial cancers.
Keywords: cutaneous squamous cell carcinoma; immunoprevention; immunotherapy; skin cancer.