Abstract LB079: Expression of C1q by macrophages and fibroblasts in tumor microenvironment is associated with invasion and metastasis of cutaneous squamous cell carcinoma

Abstract Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, with a poor prognosis for metastatic cases. We have previously demonstrated that cSCC cells in culture express components of the complement C1qr2s2 complex, specifically C1r and C1s, but not C1q. In this study, we found significantly higher mRNA levels of C1QA, C1QB, and C1QC variants 1 and 2 in cSCC tumors compared to normal skin using the Nanostring Cancer Immune Panel and qRT-PCR. Additionally, C1q production was induced in 3D spheroid co-cultures of cSCC cells, fibroblasts, and macrophages. C1q staining was detected on the surface of cSCC tumor cells, in peritumoral PDGFRbeta-positive activated fibroblasts, and in peri- and intratumoral CD68-positive macrophages using multiplexed immunofluorescence and chromogenic immunohistochemistry. Expression of C1q was higher in cSCCs compared to normal skin, actinic keratosis, and cSCC in situ. C1q expression in fibroblasts and macrophages was significantly more prevalent in metastatic primary cSCCs and cSCC metastases compared to non-metastatic cSCCs. High C1q expression in fibroblasts and macrophages in cSCC correlated with a poor prognosis. These findings provide new evidence for the role of fibroblast- and macrophage-derived C1q in the progression of cSCC. The results also suggest stromal C1q as a molecular marker for cSCC metastasis and a therapeutic target for metastatic cSCC. Citation Format: Kristina Viiklepp, Jaakko Knuutila, Liisa Nissinen, Elina Siljamäki, Pekka Rappu, Ujjwal Suwal, Teijo Pellinen, Markku Kallajoki, Seppo Meri, Jyrki Heino, Veli-Matti Kähäri, Pilvi Riihilä. Expression of C1q by macrophages and fibroblasts in tumor microenvironment is associated with invasion and metastasis of cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB079.