Investigating Components of the Innate Immune System Following Administration of a Dendritic Cell-Based Vaccine

Chan, Lily
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University of Guelph

Dendritic cell (DC)-based vaccines are an immunotherapeutic tool that has caused much excitement in cancer immunotherapy research. However, clinical trial data has demonstrated that this platform needs to be optimized to enhance clinical efficacy. Most DC immunotherapy research has focused on adaptive immunity, which has left a gap in the research and literature regarding innate immunity. Type 2 innate lymphoid cells (ILC2s), type 3 innate lymphoid cells (ILC3s), and neutrophils are all intriguing components of the innate immune system that are becoming more recognized players in cancer biology. They have all been shown to have multifaceted functional phenotypes in cancer that, depending on the context, can support pro- or anti-tumour immunity. Their potential to be influenced by external factors make these innate leukocytes ideal targets for immunotherapies. Therefore, this research sought to investigate the potential roles that these innate immune system components could play in DC-based vaccination using murine models. Following DC-based vaccination, we observed changes locally and systemically in ILC2s and ILC3s in both naïve mice and B16F10 melanoma tumor-bearing mice. We also observed changes in neutrophil populations following DC-based vaccination. Using a neutrophil-depleting antibody, we demonstrated that neutrophils primed other immune cells involved in DC-based vaccine immunobiology. The research concludes that various communications and crosstalk occur between DC-based vaccination and ILC2s, ILC3s, and neutrophils that could be important for forming anti-tumour immunity elicited by DC immunotherapies. By characterizing the communications in innate immunity during DC-based vaccination, it is possible to utilize this information to enhance the DC vaccine platform for better clinical efficacy.

immune system, innate immunity, immunotherapy, dendritic cell, neutrophil, innate lymphoid cells