MUC1 Expression Affects the Immunoflogosis in Renal Cell Carcinoma Microenvironment through Complement System Activation and Immune Infiltrate Modulation

• Published in: International journal of molecular sciences Vol. 24; no. 5; p. 4814
• Main Authors: Lucarelli, Giuseppe, Netti, Giuseppe Stefano, Rutigliano, Monica, Lasorsa, Francesco, Loizzo, Davide, Milella, Martina, Schirinzi, Annalisa, Fontana, Antonietta, Di Serio, Francesca, Tamma, Roberto, Ribatti, Domenico, Battaglia, Michele, Ranieri, Elena, Ditonno, Pasquale
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Analysis; Angiogenesis; Biomarkers; CA15-3; Cancer; Carcinoma, Renal cell; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - pathology; Care and treatment; CD59 antigen; CD8 antigen; Cells; Chemoresistance; Classical pathway; Clear cell-type renal cell carcinoma; Complement; Complement Activation; Complement C1q - metabolism; Complement component C1q; Complement component C3a; Complement component C5a; Complement receptors; Development and progression; Gene expression; Humans; Inflammation; Kidney cancer; Kidney Neoplasms - immunology; Kidney Neoplasms - pathology; kynurenine; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - immunology; Mast cells; Metabolism; Microscopy; MUC1; Mucin-1 - metabolism; Mucins; Oncology, Experimental; Pentraxins; Phenotypes; Physiological aspects; Proteins; PTX3; renal cell carcinoma; T cells; Tumor microenvironment; Tumor Microenvironment - immunology; Tumors; United Kingdom; MUC1; renal cell carcinoma; CA15-3; immune cell; PTX3; kynurenine; complement
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24054814

Mucin1 (MUC1), a glycoprotein associated with an aggressive cancer phenotype and chemoresistance, is aberrantly overexpressed in a subset of clear cell renal cell carcinoma (ccRCC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism, but its role in regulating immunoflogosis in the tumor microenvironment remains poorly understood. In a previous study, we showed that pentraxin-3 (PTX3) can affect the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system (C1q) and releasing proangiogenic factors (C3a, C5a). In this scenario, we evaluated the PTX3 expression and analyzed the potential role of complement system activation on tumor site and immune microenvironment modulation, stratifying samples in tumors with high (MUC1H) versus tumors with low MUC1 expression (MUC1L). We found that PTX3 tissue expression was significantly higher in MUC1H ccRCC. In addition, C1q deposition and the expressions of CD59, C3aR, and C5aR were extensively present in MUC1H ccRCC tissue samples and colocalized with PTX3. Finally, MUC1 expression was associated with an increased number of infiltrating mast cells, M2-macrophage, and IDO1+ cells, and a reduced number of CD8+ T cells. Taken together, our results suggest that expression of MUC1 can modulate the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system and regulating the immune infiltrate, promoting an immune-silent microenvironment.