Mitosis in Cancer Cell Increases Immune Resistance via High Expression of HLA-G and PD-L1

SIMPLE SUMMARY: Cancer results from “aggressive division” of cells, that is unchecked by the immune cells. Cancer cells express several proteins to evade the immune response. One of the main treatment against cancer is to target and block their cell division. We found that, the expression of these proteins is increased during the mitosis stage of cell division. Therefore the blockade of cell cycle in the mitotic phase may results in increased immune resistance that can further help the cancer cells in evading immune attack. ABSTRACT: Cancer is a result of “aggressive” division and uncontrolled proliferation of the abnormal cells that survive attack by immune cells. We investigated the expression of HLA-G and PD-L1 with the different stages of cancer cell division along with their role in the interaction of immune cells in vitro. Ovarian cancer (OVCAR-3) and chronic myeloid leukemia cell line (K-562) are used for this study. The correlation of protein expression with percentage of cells in each phase (G1, S and G2 phase) was evaluated through FACS. Cells were synchronized in G1, G2 and mitotic phase to evaluate gene (RT-qPCR) and protein expression (FACS). Real-time immune cell attack (RTICA) analysis with PBMCs (peripheral blood mono-nuclear cells) and cancer cells were performed. We found that cells expressing higher levels of HLA-G and PD-L1 are mainly in G2 phase and those expressing lower levels are mainly in G1 phase. Evidently, the higher expression of the two proteins was observed when synchronized in mitotic phase as compared to low expression when synchronized in G1 phase. RTICA analysis showed the presence of HLA-G delayed the lysis of the cells. In conclusion, the cancer cell can escape from immune cells in division stage that suggests the impact of mitosis index for cancer immunotherapy.