Abstract
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer that predominantly arises in chronically sun-damaged skin. Immunosuppression, genetic disorders such as xeroderma pigmentosum (XP), exposure to certain drugs and environmental noxae have been identified as major risk factors. Surgical removal of cSCC is the therapy of choice and mostly curative in early stages. However, a minority of patients develop locally advanced tumors or distant metastases that are still challenging to treat. Immune checkpoint blockade (ICB) targeting CTLA-4, PD-L1 and PD-1 has tremendously changed the field of oncological therapy and especially the treatment of skin cancers as tumors with a high mutational burden. In this review, we focus on the differences between cSCC and cutaneous melanoma (CM) and their implications on therapy, summarize the current evidence on ICB for the treatment of advanced cSCC and discuss the chances and pitfalls of this therapy option for this cancer entity. Furthermore, we focus on special subgroups of interest such as organ transplant recipients, patients with hematologic malignancies, XP and field cancerization.
Highlights
Cutaneous squamous cell carcinoma represents globally the second most common skin cancer after basal cell carcinoma (BCC) [1]
The accumulation of genetic aberrations is thought to occur in a multistep process leading to the development of actinic keratoses (AK), which eventually progress to Cutaneous squamous cell carcinoma (cSCC) [2], the risk is presumably low for single lesions
We focus on the differences between cSCC and cutaneous melanoma (CM) and the resulting implications for prognosis, summarize the current evidence on Immune checkpoint blockade (ICB) for the treatment of advanced cSCC and discuss the advantages and pitfalls of this therapy option for this cancer entity
Summary
Cutaneous squamous cell carcinoma (cSCC) represents globally the second most common skin cancer after basal cell carcinoma (BCC) [1]. Melanocytes are pigment-producing cells residing near the basal layer of the epidermis, and they are the cells of origin of melanoma [35] They are characterized by their typical shape with long protrusions (dendrites) and the presence of melanosomes [36]. In the case of melanoma, the tumor cells can acquire a migratory, invading phenotype suitable for forming metastasis by re-expressing proteins which are usually expressed exclusively during skin development This phenomenon has been demonstrated for instance for the neural crest transcription factors Brn3a and recently for MSX1 [51,52], which both contribute to melanoma progression. Both skin cancer entities comprise tumors with a high mutational burden which seems to be a major reason for a good response to ICB [55]
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