%0 Journal Article
%T Radiation-based immunogenic vaccine combined with a macrophage "checkpoint inhibitor" for boosting innate and adaptive immunity against metastatic colon cancers.
%A Xu H
%A Qin X
%A Guo Y
%A Zhao S
%A Feng X
%A Zhang R
%A Tian T
%A Kong L
%A Yang C
%A Zhang Z
%J Acta Pharm Sin B
%V 14
%N 5
%D 2024 May
%M 38799631
%F 14.903
%R 10.1016/j.apsb.2024.02.015
%X Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors. Especially, X-ray- induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants. However, we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines, which can specifically bind with the MerTK receptor on macrophages, acting as a "checkpoint" to facilitate immune silence in the tumor microenvironment. Therefore, we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250, a macrophage MerTK "checkpoint inhibitor," for treating peritoneal carcinomatosis in colon cancer. By incorporating UNC2250 into the treatment regimen, immunosuppressive efferocytosis of macrophages, which relies on MerTK-directed recognition of phosphatidylserine on vaccines, was effectively blocked. Consequently, the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages, thereby simultaneously eliciting robust adaptive and innate immunity. This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.