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Cutaneous squamous cell carcinoma (cSCC), is a malignant proliferation of skin epithelial cells, represents between 20% - 50% of all skin cancers. It is the second most common non-melanoma skin cancer after basal cell carcinoma.
Cutaneous squamous cell carcinoma (cSCC) is caused predominantly by sun (ultraviolet radiation, UV) exposure. The increase in incidence worldwide is likely to be due to changes in lifestyle, people living longer and clothing resulting in more UV exposure of the skin. It is also prevalent in immunosuppressed patients, older age group and those with fair skin.
Although the majority of cSCCs are successfully eradicated by surgical excision with good prognosis, a subset of cSCC possesses features associated with a higher likelihood of recurrence, metastasis, and death. cSCC accounts for 20% of cutaneous malignancies and about 75% of all deaths due to skin cancer, excluding melanoma.
Scientific data suggest involvement of C5a in tumour formation and progression. Expression of the receptors for C5a (C5aR) is increased in many epithelial tumours, including cSCC. C5a is expressed at high levels in the tumor environment and may directly promote tumor growth and, through several mechanisms, metastasis.
There are no other treatment options for patients with PD-(L)1-resistant or refractory cSCC. An anti-C5a therapy may reverse resistance to PD-1 or PD-L1 inhibitor therapy.