Background: Cytoskeleton-associated protein 2-like (CKAP2L) has been implicated in various malignancies, including ovarian cancer. However, its role in modulating the immune microenvironment of ovarian cancer remains poorly understood. This study aimed to investigate the role of CKAP2L in regulating ovarian cancer cell proliferation, migration, and apoptosis.

Methods: The impact of CKAP2L knockdown on ovarian cancer cells and the immune microenvironment was examined. CKAP2L was silenced in ovarian cancer cell lines, and subsequent effects on proliferation, migration, and apoptosis were assessed. Macrophage polarization differentiated from peripheral blood mononuclear cells (PBMCs) co-cultured with ovarian cancer cells was evaluated. Expression of the adenosine A2A receptor (ADORA2A) in macrophages, and interleukin-1β (IL-1β), interleukin-10 (IL-10) and vascular endothelial growth factor (VEGF) levels in ovarian cancer cells, were analyzed using western blotting and cytokine antibody arrays.

Results: CKAP2L knockdown significantly reduced proliferation and migration of ovarian cancer cell, while promoting apoptosis (p < 0.01). Flow cytometry revealed that CKAP2L knockdown inhibited M2-type and promoted M1-type polarization of PBMC-derived macrophages induced by ovarian cancer cells (p < 0.001). Furthermore, CKAP2L knockdown reduced ADORA2A expression in macrophages, increased IL-1β secretion, and reduced IL-10, VEGF secretion by ovarian cancer cells (p < 0.01).

Conclusions: CKAP2L promotes ovarian cancer progression by enhancing proliferation and migration while suppressing apoptosis. It also regulates the immune microenvironment by influencing macrophage polarization and cytokine secretion. These findings highlight the pivotal role of CKAP2L in the pathogenesis of ovarian cancer and support its potential as a therapeutic target for regulating tumor growth and immune responses.