Researchers at Washington University School of Medicine in St. Louis announced on April 17 that they have discovered unexpected immune pathways involved in the response to mRNA cancer vaccines, according to a study published April 15 in Nature.
The findings could influence how future mRNA cancer vaccines are designed and may help improve their effectiveness. The research suggests that multiple types of dendritic cells, not just one as previously thought, can stimulate T cells to attack tumor cells after vaccination.
In experiments using mouse models, scientists found that even when classical type 1 dendritic cells (cDC1s) were absent, immunization with an mRNA vaccine still triggered strong T-cell responses and enabled the animals to clear sarcoma tumors. This indicates that another subtype of dendritic cell must be involved in activating the immune system's anti-tumor response.
Further investigation revealed that cDC2s, a related subtype of dendritic cell, also play a role in generating an immune response from T cells and preventing tumor growth. The study showed that both cDC1s and cDC2s contribute to stopping cancer following mRNA vaccination, though each appears to prime T cells with slightly different molecular characteristics. Additional research suggested that cDC2s activate T cells through a process known as "cross dressing," where other cells process the protein produced from the vaccine instructions and transfer it onto cDC2s for presentation to T cells.
William E. Gillanders said: "This work uncovers a new way mRNA vaccines engage the immune system - through both cDC1 and cDC2 - which helps explain their power and gives researchers concrete targets for making future mRNA cancer vaccines more effective." He added: "It could improve vaccine formulation and dosing, potentially explain why some patients respond better to vaccines than others and guide strategies for making vaccines more effective."
The broader implications of this research may include improved outcomes for patients receiving mRNA-based therapies against various cancers as scientists refine vaccine design based on these findings.
