Neutrophils in Dendritic Cell-Based Cancer Vaccination: The Potential Roles of Neutrophil Extracellular Trap Formation

Int J Mol Sci. 2023 Jan 4;24(2):896. doi: 10.3390/ijms24020896.

Abstract

Neutrophils have conflicting roles in the context of cancers, where they have been associated with contributing to both anti-tumor and pro-tumor responses. Their functional heterogenicity is plastic and can be manipulated by environmental stimuli, which has fueled an area of research investigating therapeutic strategies targeting neutrophils. Dendritic cell (DC)-based cancer vaccination is an immunotherapy that has exhibited clinical promise but has shown limited clinical efficacy. Enhancing our understanding of the communications occurring during DC cancer vaccination can uncover opportunities for enhancing the DC vaccine platform. There have been observed communications between neutrophils and DCs during natural immune responses. However, their crosstalk has been poorly studied in the context of DC vaccination. Here, we review the dual functionality of neutrophils in the context of cancers, describe the crosstalk between neutrophils and DCs during immune responses, and discuss their implications in DC cancer vaccination. This discussion will focus on how neutrophil extracellular traps can influence immune responses in the tumor microenvironment and what roles they may play in promoting or hindering DC vaccine-induced anti-tumor efficacy.

Keywords: NET; dendritic cell vaccination; immunotherapy; neutrophils; plasticity.

Publication types

  • Review

MeSH terms

  • Cancer Vaccines*
  • Dendritic Cells
  • Extracellular Traps*
  • Hematologic Neoplasms*
  • Humans
  • Neoplasms* / pathology
  • Neutrophils
  • Sarcoma*
  • Tumor Microenvironment
  • Vaccination

Substances

  • Cancer Vaccines

Grants and funding

Funding was provided to K.K. by two Operating Grants from the Pet Trust Foundation to K.K. (#054725 and #055676). Funding was provided to B.W.B. by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (#436264), 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), and an Operating Grant from the Cancer Research Society (#843296). Stipend funding was provided to L.C. by a NSERC Postgraduate Scholarship—Doctoral and an Ontario Veterinary College Scholarship.