Host: The Japanese Pharmacological Society
Name : The 95th Annual Meeting of the Japanese Pharmacological Society
Number : 95
Location : Fukuoka
Date : March 07, 2022 - March 09, 2022
Cancers evade immunity by multiple mechanisms. Myeloid-derived suppressor cells (MDSCs) have been shown to be involved in immunosuppression in cancer patients. They are suggested to be increased and activated by tumor microenvironment. Subpopulations of MDSCs have been shown to be monocytes/macrophage-lineage cell. In addition, subpopulations of tumor-associated macrophages have also been shown to suppress inflammation and immune response in tumors, suggesting that tumor microenvironment may educate monocytes/macrophages to acquire the immune regulatory function. To test this hypothesis, we first injected a mixture of bone marrow-derived macrophages (BMDMs) and LL/2 lung cancer cells subcutaneously into mice. We found that BMDMs increased tumor growth. To further analyze, we cocultured BMDMs with LL/2 cells. Interestingly, coculturing with LL/2 dramatically increased expression of Cd274, encoding an immune checkpoint protein PD-L1. They also increased Vegf (vascular endothelial growth factor) expression. These results suggest that LL/2-educated BMDMs may promote tumor growth. Indeed, LL/2-educated BMDMs suppressed activation of CD8⁺T cells, indicating they acquired immune suppressive activity. Our data support the notion that tumor microenvironment educate macrophages so that they support tumor survival and growth.
