Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response

Abstract

Background: Non-melanoma skin cancer (NMSC) stands as an umbrella term for common cutaneous malignancies, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together with rarer cutaneous cancers, such as Merkel cell carcinoma (MCC) and other forms of adnexal cancers. The majority of NMSCs can be successfully treated with surgery or radiotherapy, but advanced and metastatic stages may require systemic approaches such as immunotherapy with immune checkpoint inhibitors (ICIs). Summary: Since immunotherapy is not effective in all patients and can potentially lead to severe adverse effects, an important clinical question is how to properly identify those who could be suitable candidates for this therapeutic choice. In this paper, we review the potential features and biomarkers used to predict the outcome of ICIs therapy for NMSCs. Moreover, we analyze the role of immunotherapy in special populations, such as the elderly, immunocompromised patients, organ transplant recipients, and subjects suffering from autoimmune conditions. Key messages: Many clinical, serum, histopathological, and genetic features have been investigated as potential predictors of response in NMSCs treated with ICIs. Although this field of research is very promising, definitive, cost-effective, and reproducible biomarkers are still lacking and further efforts are needed to validate the suggested predictors in larger cohorts.

Lower leg reconstruction after resection of a squamous cell carcinoma on necrobiosis lipoidica with a pedicled fibula and an extended anterolateral thigh flap – A case report

“…Even if surgery is the rst-choice treatment for cSCC, immune checkpoint inhibitors gained a leading role in the treatment of locally advanced and metastatic cSCCs. In our case, surgical therapy was preferred because the tumor was still resectable and an anti-PD1 therapy failure could not be ruled out in a cSCC arising in NL [7].…”

Lower leg reconstruction after resection of a squamous cell carcinoma on necrobiosis lipoidica with a pedicled fibula and an extended anterolateral thigh flap—a case report

“…Even if surgery is the first-choice treatment for cSCC, immune checkpoint inhibitors gained a leading role in the treatment of locally advanced and metastatic cSCCs. In our case, surgical therapy was preferred because the tumor was still resectable and an anti-PD1 therapy failure could not be ruled out in a cSCC arising in NL [ 7 ].…”

Molecular Mechanisms and Targeted Therapies of Advanced Basal Cell Carcinoma

“…Again, PD-1 binds two ligands, the PD-L1 and PD-L2 on tumor cells [ 140 ]. PD-L1 expression is expected to be a biomarker for PD-1 inhibition therapy and was reported to be a positive predictor of pembrolizumab for cutaneous squamous cell carcinomas [ 171 , 172 ]. However, as for BCCs, PD-L1 expression was not associated with the response to cemiplimab [ 146 , 156 , 171 ].…”