Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma

PLoS One. 2013;8(2):e57114. doi: 10.1371/journal.pone.0057114. Epub 2013 Feb 20.

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T cell immunity in tumor-bearing hosts. In patients with colon cancer, MDSCs have recently been described as Lin(-/low)HLA-DR(-)CD11b(+)CD33(+) cells correlating with cancer stage, metastasis and chemotherapy response. To learn in more detail the dynamic change and clinical relevance of circulating and tumor-infiltrating Lin(-/low)HLA-DR(-)CD11b(+)CD33(+) MDSC in colorectal cancer, we harvested the blood from 64 patients with varying stage of colorectal cancer and tumor and matched paraneoplastic tissues from 5 patients with advanced colorectal cancer, subjected them to multicolor flow cytometric analysis of percentage, absolute number and phenotype of MDSC and finally characterized their immunosuppressive functions. Our results demonstrate that peripheral blood from colorectal cancer patients contains markedly increased percentage and absolute number of Lin(-/low)HLA-DR(-)CD11b(+)CD33(+) MDSCs compared with healthy individuals, and this increase is closely correlated with clinical cancer stage and tumor metastasis but not primary tumor size and serum concentrations of cancer biomarker. A similar increase of MDSCs was also observed in the tumor tissues. Phenotyping MDSCs shows that they express high CD13 and CD39, low CD115, CD117, CD124 and PD-L1, and devoid of CD14, CD15 and CD66b, reminiscent of precursor myeloid cells. MDSCs from cancer patients but not healthy donors have the immunosuppressive activity and were able to inhibit in vitro autologous T-cell proliferation. Collectively, this study substantiates the presence of increased immunosuppressive circulating and tumor-resident Lin(-/low)HLA-DR(-)CD11b(+)CD33(+) MDSCs in patients with colorectal cancers correlating with cancer stage and metastasis, and suggests that pharmacologic blockade of MDSCs should be considered in future clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Surface / metabolism
  • CD11b Antigen / metabolism
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • HLA-DR Antigens / metabolism
  • Humans
  • Immunophenotyping
  • Immunosuppression
  • Male
  • Middle Aged
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Sialic Acid Binding Ig-like Lectin 3 / metabolism

Substances

  • Antigens, Surface
  • CD11b Antigen
  • HLA-DR Antigens
  • Sialic Acid Binding Ig-like Lectin 3

Grant support

This work was supported by the the Beijing Natural Science Foundation (7133254 to BZ), the Beijing Nova Program (to ZJW), the National Natural Science Foundation of China (No. 30901380/C081501 to HFW) and the Shanghai Morning Light Program (09CG36 to HFW). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.