Comprehensive analysis of different tumor cell-line produced soluble mediators on the differentiation and functional properties of monocyte-derived dendritic cells

PLoS One. 2022 Oct 4;17(10):e0274056. doi: 10.1371/journal.pone.0274056. eCollection 2022.

Abstract

Developing dendritic cells (DCs) from monocytes is a sensitively regulated process. One possible way for cancers to avoid immune recognition and antitumor response is the modulation of DC differentiation. Although several studies are available on the examination of tumor-associated macrophages, a comprehensive analysis focusing on the effects of tumor-formed DCs is not known to date. We provide a comparative analysis of the tumor-edited-monocyte derived DCs differentiated in the presence of adenocarcinomas (MDA, HT29, HeLa)- and primary (WM278, WM983A) or metastatic (WM1617, WM983B) melanomas. The immunomodulatory effect of tumors is mediated at least partly by secreted mediators. We investigated the impact of tumor cell-derived conditioned media on the differentiation of DCs from CD14+ monocytes, sequentially determining the phenotype, cytokine production, phagocytic, and the T cell polarizing capacity of moDCs. We completed our observations by analyzing our data with bioinformatic tools to provide objective correlations between phenotypical and functional properties of different tumor-educated moDCs. The correlation analysis revealed significant differences in the characteristics of adenocarcinomas- or melanomas-edited moDCs. We highlight the functional differences in the properties of moDCs differentiated in the presence of various cancer cell lines. We offer new information and options for the in vitro differentiation protocols of various tumor-conditioned moDCs. Our results confirm that various immunomodulatory properties of different tumor cell lines result in multiple manipulations of DC differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / metabolism
  • Cell Differentiation
  • Cell Line, Tumor
  • Cells, Cultured
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology
  • Cytokines / metabolism
  • Dendritic Cells
  • Humans
  • Melanoma* / metabolism
  • Monocytes / metabolism

Substances

  • Culture Media, Conditioned
  • Cytokines

Grants and funding

The work was supported by GINOP-2.3.2-15-2016-00050 project and NTP-NFTÖ-21 and NTP-NFTÖ-22. The work was also supported by National Research, Development and Innovation Office (K125224 and K 142930).