YKL-40 inhibits melanoma progression and metastasis by inducing immune cell infiltration in a mouse model

YKL-40 is a glycoprotein that has been extensively studied due to its elevated expression in numerous solid tumors, and its expression is altered in melanoma, where its levels in tumor tissues are notably lower compared with those in normal skin tissues. Patients with melanoma exhibiting high YKL-40 expression have improved survival rates, suggesting a potential tumor-suppressive function of YKL-40 in melanoma. The present investigation into the ectopic expression of YKL-40 in human (A375) and murine (B16F10) melanoma cell lines demonstrated a consequential decrease in cell proliferation, migration and invasion. Furthermore, YKL-40 overexpression was associated with suppressed tumor growth in a subcutaneous melanoma mouse model and diminished tumor cell metastasis in a pulmonary metastasis model. RNA-sequencing analysis revealed that YKL-40 overexpression led to the upregulation of immune cell infiltration-related signaling pathways, including cytokine receptor interactions, natural killer cell-mediated cytotoxicity, and T and B lymphocyte receptor signaling. These findings highlight the potential of YKL-40 as a regulator of tumor-immune interactions in melanoma, highlighting its prospective utility in immunotherapy-based treatment strategies for melanoma.