INTRODUCTION
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with increasing incidence rates worldwide.1 While most cases are successfully treated with surgical excision or radiation therapy, a subset of patients develop locally advanced cSCC (laCSCC) or metastatic cSCC (mCSCC) that is not amenable to standard treatments, presenting significant therapeutic challenges.2,3
cSCC features a high tumor mutational burden (TMB) and elevated prevalence in immunosuppressed individuals, indicating a circumvention of immune surveillance. The programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint pathway plays a critical role in tumor immune evasion in cSCC. PD-1 is an inhibitory receptor primarily found on T cells that, when bound by its ligands, PD-L1 and PD-L2, found on antigen-presenting cells and many cancer cells, restrains T cells from full activation and proliferation, thereby suppressing antitumor responses. cSCC tumors exploit this pathway by overexpressing PD-L1 on tumor cells, which interacts with PD-1 receptors on T cells to promote T cell inhibition and immune evasion.4 These characteristics make advanced cSCC an exceptionally prime candidate for immunotherapy.2,5-10
The treatment landscape for advanced cSCC has been transformed by the introduction of immune checkpoint inhibitors (ICIs). Cemiplimab (a fully human PD-1 monoclonal antibody) and pembrolizumab (a humanized PD-1 monoclonal
cSCC features a high tumor mutational burden (TMB) and elevated prevalence in immunosuppressed individuals, indicating a circumvention of immune surveillance. The programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint pathway plays a critical role in tumor immune evasion in cSCC. PD-1 is an inhibitory receptor primarily found on T cells that, when bound by its ligands, PD-L1 and PD-L2, found on antigen-presenting cells and many cancer cells, restrains T cells from full activation and proliferation, thereby suppressing antitumor responses. cSCC tumors exploit this pathway by overexpressing PD-L1 on tumor cells, which interacts with PD-1 receptors on T cells to promote T cell inhibition and immune evasion.4 These characteristics make advanced cSCC an exceptionally prime candidate for immunotherapy.2,5-10
The treatment landscape for advanced cSCC has been transformed by the introduction of immune checkpoint inhibitors (ICIs). Cemiplimab (a fully human PD-1 monoclonal antibody) and pembrolizumab (a humanized PD-1 monoclonal
