https://doi.org/10.1016/j.apsb.2024.02.015
This new article publication from Acta Pharmaceutica Sinica B, discusses how the use of a radiation-based immunogenic vaccine combined with a macrophage "checkpoint inhibitor" can boost innate and adaptive immunity against metastatic colon cancers.
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.
The authors of this article note 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, a novel strategy was developed 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.
Keywords: Immunogenic cell death; Cancer vaccine; X-ray; Efferocytosis; Macrophage; STING; Adaptive immunity; Innate immunity
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383524000534-ga1.jpg
Frozen dying tumor cells (FDT) combined with efferocytosis inhibitors can mobilize dendritc cells and macrophages simultaneously, thereby eliciting robust innate and adaptive immunity against peritoneal carcinomatosis in colon cancer.
