Pankreas Kanserinde Nektin Ailesi Molekülleri ile NK Hücre Fonksiyonları Arasındaki İlişki

Abstract

Pancreatic cancer is one of the most lethal cancers due to late diagnosis and limited treatment options. In this cancer, the tumor microenvironment consists of a complex combination of immune cells and stromal structures, affecting both tumor development and immune defense mechanisms. Natural killer (NK) cells play an important role in the defense against tumor cells, especially through their cytotoxic activity. However, the immunosuppressive microenvironment of pancreatic cancer may limit the functionality of NK cells. Therefore, understanding the interactions of NK cells with tumors is critical for the development of novel therapeutic approaches. In this study, the interaction of NK-92 cells and pancreatic cancer cell line BxPC-3 was examined in a six-day co-culture model. During the co-culture process, gene expression levels of Nectin family and PVR molecules, NK cell receptors (DNAM-1 TIGIT, PVRIG and CD96) and cytotoxicity molecules (CD107a, Perforin, Granzyme B) were analyzed. It was observed that DNAM-1 family receptors and ligands exhibited different behaviors during the first 36 hours and beyond during co-culture. The expression of the activation receptor DNAM-1 increased during the first five days, while the expression of the inhibitory receptors TIGIT and CD96 decreased after 36 hours. PVRIG expression decreased over time. The cytotoxicity of NK cells during co-culture was high until 72 hours and then decreased. These changes were associated with correlations between the expression of NK cell surface receptors and ligands on cancer cells. Our study demonstrates that DNAM-1 family receptors and ligands interact in a complex manner and that NK cell functions are regulated depending on these relationships. In conclusion, the PVR molecule, a common ligand of DNAM-1 TIGIT and CD96 receptors, was found to play an important role in the regulation of NK cell functions. With these findings, we aim to contribute to the identification of new targets for NK cell-based therapies for pancreatic cancer.