298 Macrophage-derived C1q in cutaneous squamous cell carcinoma

Incidence of cutaneous squamous cell carcinoma (cSCC) is increasing worldwide. Previous studies have shown the role of tumor cell-derived complement components in progression of cSCC. Here, the expression of C1q, the initial classical pathway component, was determined with Nanostring Cancer Immune Panel and qRT-PCR. In cSCC tumors the mRNA levels of C1q subunits C1QA, C1QB, and C1QC variant 1 and 2 were significantly higher than in normal skin. Multiplexed fluorescence immunohistochemistry revealed that in cSCCs (n=413) the C1q expression was significantly higher compared to actinic keratosis, (n= 69) or cSCCin situ (n=70) in vivo. The staining was localized to tumor associated macrophages and epithelial cells and the expression was associated with the risk of metastasis of primary cSCC. The results were verified with immunohistochemistry. Membranous tumor cell specific staining of C1q was noted in cSCCs (n=228) and the staining was significantly weaker in actinic keratosis (n=40), cSCC in situ(n=45), seborrheic keratoses (n=17) or normal skin (n=92). Most of the peri- and intratumoral macrophages stained strongly for C1q and the expression was noted also in activated stromal fibroblasts. Mass spectrometry-based proteomic analysis showed that C1QA, C1QB and C1QC are significantly upregulated in spheroid co-cultures containing cSCC cells, fibroblasts and M2 macrophages in comparison to control co-cultures without macrophages. These results suggest that tumor associated macrophages and fibroblasts are the main source of C1q in cSCC. C1q could serve as a molecular marker for the progression and metastasis of cSCC and as a new therapeutic target in metastatic cSCC.