Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. The incidence of cSCC and its precancerous forms is increasing globally. Previous studies have shown a tumor promoting function of complement system in cSCC. We have shown that C1r and C1s, components of the classical pathway, are upregulated in cSCC cells compared to normal keratinocytes and promote the growth, vascularization and invasion of cSCC tumors in vivo. Here we have investigated the expression of classical pathway component C1q in cSCC. The expression of complement genes in RNA samples of cSCC tumors and normal skin in vivo was determined with Nanostring Cancer Immune Panel and qRT-PCR. These results showed, that the mRNA levels for C1QA, C1QB, C1QC variant 1 and C1QC variant 2 were significantly higher in cSCC tumors than in normal skin. Immunohistochemical analysis for C1q showed stronger specific cell surface-associated staining intensity in cSCCs (n=262) than in premalignant epidermal lesions (actinic keratoses, n=38), in cSCC in situ (n=45), benign epidermal papillomas (seborrheic keratoses, n=17) and normal skin (n=95) in vivo. Prominent expression of C1q was detected in macrophages in the peritumoral microenvironment and in intratumoral macrophages in cSCC tumors. In addition, expression of C1q was detected in stromal fibroblasts in cSCCs. These results provide new evidence for the role of macrophage-derived C1q in the progression of cSCC to invasive stage. The results suggest C1q as a molecular marker for the progression of cSCC and as a potential new therapeutic target for advanced and metastatic cSCC.

Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. The incidence of cSCC and its precancerous forms is increasing globally. Previous studies have shown a tumor promoting function of complement system in cSCC. We have shown that C1r and C1s, components of the classical pathway, are upregulated in cSCC cells compared to normal keratinocytes and promote the growth, vascularization and invasion of cSCC tumors _in vivo_. Here we have investigated the expression of classical pathway component C1q in cSCC. The expression of complement genes in RNA samples of cSCC tumors and normal skin _in vivo_ was determined with Nanostring Cancer Immune Panel and qRT-PCR. These results showed, that the mRNA levels for C1QA, C1QB, C1QC variant 1 and C1QC variant 2 were significantly higher in cSCC tumors than in normal skin. Immunohistochemical analysis for C1q showed stronger specific cell surface-associated staining intensity in cSCCs (n=262) than in premalignant epidermal lesions (actinic keratoses, n=38), in cSCC _in situ_ (n=45), benign epidermal papillomas (seborrheic keratoses, n=17) and normal skin (n=95) _in vivo_. Prominent expression of C1q was detected in macrophages in the peritumoral microenvironment and in intratumoral macrophages in cSCC tumors. In addition, expression of C1q was detected in stromal fibroblasts in cSCCs. These results provide new evidence for the role of macrophage-derived C1q in the progression of cSCC to invasive stage. The results suggest C1q as a molecular marker for the progression of cSCC and as a potential new therapeutic target for advanced and metastatic cSCC.

ESDR489 - Expression of C1q by macrophages in tumor microenvironment is associated with progression of cutaneous squamous cell carcinoma

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.