Dendritic Cell-Based Vaccines Recruit Neutrophils to the Local Draining Lymph Nodes to Prime Natural Killer Cell Responses

Cells. 2022 Dec 28;12(1):121. doi: 10.3390/cells12010121.

Abstract

Dendritic cell (DC)-based cancer vaccines are a form of immunotherapy that activates the innate and adaptive immune systems to combat cancers. Neutrophils contribute to cancer biology and have the potential to be exploited by immunotherapeutic platforms to enhance anti-tumor immune responses. We previously showed that DC vaccines elicit the expansion of mouse interferon (IFN)γ-producing mature natural killer (NK) cells to elevate anti-tumor responses. Here, we demonstrate the rapid recruitment of neutrophils to the draining lymph nodes of DC-vaccinated mice. This was accompanied by an increase in the total number of NK cells producing IFNγ and expressing CD107a, a marker of degranulation that demonstrates NK cell functional activity. Furthermore, the depletion of neutrophils in DC-immunized mice resulted in decreased numbers of NK cells in draining lymph nodes compared to the controls. Interestingly, the increased number of IFNγ- and CD107a-expressing NK cells in DC-immunized mice was not detected in mice depleted of neutrophils. Further investigations showed that DC vaccines induced IFNγ- and TNFα-producing CD8+ T cells that also expressed CD107a, but depletion of neutrophils did not have any impact on the CD8+ T cell population. Our findings suggest that neutrophil-mediated anti-tumor immunity induced by a DC vaccine platform could be targeted to provide innovative strategies to enhance its clinical efficacy.

Keywords: crosstalk; dendritic cell vaccine; immunobiology; natural killer cells; neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells
  • Killer Cells, Natural
  • Lymph Nodes
  • Mice
  • Neoplasms*
  • Neutrophils
  • Vaccines*

Substances

  • Vaccines

Grants and funding

Operating funds were provided by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (#436264) and an Innovation Grant that was jointly funded by the Canadian Cancer Society Research Institute (#705965) and the Canadian Institutes of Health Research–Institute of Cancer Research (#160399) (awarded to B.W.B.). Stipend funding was provided by an Ontario Graduate Scholarship (OGS), NSERC Postgraduate Scholarship—Doctoral, and Ontario Veterinary College Scholarship (L.C.).