LINC01119 encapsulated by cancer-associated adipocytes-derived exosomes promotes M2 polarization of macrophages to induce immune escape in ovarian cancer in a 3D co-culture cell-based model.

Abstract

In the present study, we sought to clarify the role of LINC01119 delivered by cancer-associated adipocytes (CAAs)-derived exosomes (CAA-Exo) and its mechanistic actions in ovarian cancer (OC). The expression of LINC01119 was determined in OC, and the relationship between LINC01119 expression and the prognosis of OC patients was analyzed. Besides, 3D co-culture cell models were constructed using green fluorescent protein-labeled OC cells and red fluorescent protein-labeled mature adipocytes. Mature adipocytes were co-cultured with OC cells to induce CAA. Macrophages treated with CAA-Exo were co-cultured with SKOV3 cells following ectopic expression and depletion experiments of LINC01119 and SOCS5 to detect M2 polarization of macrophages, PD-L1 level, proliferation of CD3+ T cells, and cytotoxicity of T cells to SKOV3 cells. LINC01119 was elevated in the plasma Exo of OC patients, which was related to shorter overall survival in OC patients. LINC01119 expression was increased in CAA-Exo, which could upregulate SOCS5 in OC. Finally, CAA-Exo carrying LINC01119 induced M2 polarization of macrophages to promote immune escape in OC, as evidenced by inhibited CD3+ T cell proliferation, increased PD-L1 level, and attenuated T cell toxicity to SKOV3 cells. In conclusion, the key findings of the current study demonstrated the promoting effects of CAA-Exo containing LINC01119 mediating SOCS5 on M2 polarization of macrophages and immune escape in OC.