Abstract LB207: C5ar1 is a novel biomarker and potential therapeutic target in advanced cutaneous squamous cell carcinoma

Abstract Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer and the metastatic disease is associated with poor prognosis. At present, there are no established molecular markers to predict the metastasis risk and prognosis of patients with primary cSCC. Recently, the role of specific complement components in the progression of cSCC has been shown. Here, we have examined the role of complement C5a receptor C5aR1 in the progression and metastasis of cSCC. The results show that the expression of C5aR1 is increased in cSCC cells in 3D spheroid coculture model in the presence of fibroblasts and that treatment with recombinant C5a increases invasion of cSCC cells in this model. Staining for C5aR1 was detected on the surface of tumor cells in the invasive edge of human cSCC xenograft tumors in vivo. Staining of metastatic and non-metastatic primary human cSCCs, premalignant epidermal lesions and normal skin for C5aR1 with multiplexed fluorescence and chromogenic immunohistochemistry revealed stronger expression of C5aR1 on surface of cSCC tumor cells compared to epidermal cells in cSCC in situ, actinic keratosis and normal skin. Increased expression of C5aR1 on tumor cell surface was associated with the metastasis risk of primary cSCCs and independently predicted poor disease-specific survival of patients with primary cSCC. These results reveal the role of C5aR1 in cSCC progression and identify C5aR1 as a novel biomarker for metastasis risk and poor prognosis of patients with cSCC. The results also suggest C5aR1 as a novel therapeutic target for treatment of locally advanced and metastatic cSCC. Citation Format: Lauri Heiskanen, Liisa Nissinen, Elina Siljamäki, Jaakko Knuutila, Teijo Pellinen, Markku Kallajoki, Jyrki Heino, Pilvi Riihilä, Veli-Matti Kähäri. C5ar1 is a novel biomarker and potential therapeutic target in advanced cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB207.