Abstract
Epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer with high mortality rates in the advanced stage. Chronic inflammation is a recognized risk factor for cSCC progression and the complement system, as a part of innate immunity, belongs to the microenvironment of tumors. The complement system is a double-edged sword in cancer, since complement activation is involved in anti-tumor cytotoxicity and immune responses, but it also promotes cancer progression directly and indirectly. Recently, the role of several complement components and inhibitors in the regulation of progression of cSCC has been shown. In this review, we will discuss the role of complement system components and inhibitors as biomarkers and potential new targets for therapeutic intervention in cSCC.
Highlights
Keratinocyte-derived non-melanoma skin cancers (NMSC) are the most common human malignancies and their incidence is increasing worldwide [1]
These results suggest that expression of Complement factor I (CFI) and complement factor H (CFH) by Cutaneous squamous cell carcinomas (cSCC) cells protects cSCC tumor cells from complement-mediated cell lysis
The complement system is a complex network of effectors, receptors, and regulators with many different roles
Summary
Keratinocyte-derived non-melanoma skin cancers (NMSC) are the most common human malignancies and their incidence is increasing worldwide [1]. The prognosis in the metastatic disease with current treatments is generally poor and there is a need for biomarkers to predict the risk of recurrence and metastasis of primary cSCC [3]. The majority of patients with cSCC present with several concurrent AK lesions and, on the other hand, only a small percentage of these precursor lesions develop into invasive cSCC Both the risk of developing another primary cSCC and nodal metastasis increase significantly with the number of current and prior cSCC lesions [33]. The immune checkpoint inhibitor and the programmed cell death protein-1 (PD-1) blocking monoclonal antibody cemiplimab has been approved by FDA for treating patients with metastatic or locally advanced cSCC, who are not candidates for curative surgery or curative radiation therapy [42]
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