KIF2C regulates macrophage M2 polarization and DLBCL progression by regulating the STAT3/IL-10 axis

Abstract

KIF2C is an oncogene highly expressed in various malignancies, but its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. In this study, THP-1 cells were stimulated to differentiate into M0, M1, and M2 macrophages using the culture medium of OCI-LY3 DLBCL cells. KIF2C expression was upregulated during M2 polarization. Knockdown or overexpression of KIF2C in THP-1 cells revealed that KIF2C promoted M2 but not M1 polarization. Whether in the co-culture of THP-1_M0 cells with altered KIF2C levels and OCI-LY3 cells, or in OCI-LY3 cells with altered KIF2C levels. KIF2C knockdown inhibited OCI-LY3 proliferation, migration, and invasion, and promoted apoptosis. In contrast, KIF2C overexpression enhanced M2 polarization and tumor-promoting behaviors. Mechanistically, KIF2C knockdown reduced p-STAT3 (Tyr705) levels in macrophages. Application of STAT3 agonist colivelin TFA restored IL-10 expression and M2 polarization. KIF2C knockdown in tumor cells inhibited their growth and viability, both in vitro and in a subcutaneous xenograft model, in which M2 macrophage polarization, IL-10 expression, and tumor progression were reduced. These findings suggest that KIF2C in macrophages and/or tumor cells regulates DLBCL-associated M2 macrophage polarization and tumor progression through the STAT3/IL-10 axis, highlighting KIF2C as a potential therapeutic target in DLBCL.