Correlation analysis of the proportion of monocytic myeloid-derived suppressor cells in colorectal cancer patients

PLoS One. 2020 Dec 28;15(12):e0243643. doi: 10.1371/journal.pone.0243643. eCollection 2020.

Abstract

Monocytic myeloid-derived suppressor cells (mMDSCs) are a class of immunosuppressive immune cells with prognostic value in many solid tumors. It is reported that the proportion of mMDSCs in the peripheral blood can be a predictive marker for response to cancer immunotherapy. In this study, we performed a correlation analysis of the proportion of mMDSCs in freshly-drawn peripheral blood, levels of plasma proteins, and demographic factors in colorectal cancer (CRC) patients, to find factors that could be used to predict mMDSC proportions. Freshly-drawn mMDSCs were measured using flow cytometry on peripheral blood mononuclear cells (PBMCs) from healthy donors (n = 24) and CRC patients (n = 78). The plasma concentrations of 29 different cytokines, chemokines, growth factors, and enzymes were measured using a multiplex assay or enzyme-linked immunosorbent assay. Correlation analysis to find mMDSC-associated factors was conducted using univariate and multivariate models. In univariate correlation analysis, there were no plasma proteins that were associated with mMDSC proportions in CRC patients. In multivariate analysis, considering all variables including age, sex, and plasma proteins, levels of inducible nitric acid synthase (iNOS) (p = 0.013) and platelet-derived growth factor (PDGF)-BB (p = 0.035) were associated with mMDSC proportion in PBMCs (mMDSC proportion [%] = 0.2929 - 0.2389 * PDGF-BB + 0.3582 * iNOS) (p < 0.005, r = 0.32). Measuring the plasma concentrations of iNOS and PDGF-BB may be useful in predicting the proportion of mMDSCs in CRC patients' peripheral blood. Further research is required to establish and validate these predictive factors. Data registration Patient data were registered in an anonymization system at Tsukuba Clinical Research & Development Organization (T-CReDO).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cells, Cultured
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / pathology*
  • Cytokines / blood
  • Female
  • Flow Cytometry
  • Humans
  • Leukocytes, Mononuclear / pathology*
  • Male
  • Middle Aged
  • Myeloid-Derived Suppressor Cells / pathology*

Substances

  • Cytokines

Associated data

  • figshare/10.6084/m9.figshare.13006922

Grants and funding

The authors declare that, other than income received from our primary employers, no financial support or compensation has been received for this research and that there are no personal conflicts of interest to declare. This research did not receive any specific grant from funding agencies in the public, commercial, or not for profit sectors. The funding organization (Astellas Pharma, Inc.) did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of author’s salaries and/or research materials.