Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma

World J Gastroenterol. 2012 Jul 7;18(25):3303-9. doi: 10.3748/wjg.v18.i25.3303.

Abstract

Aim: To investigate the frequency and clinical significance of the myeloid-derived suppressor cells (MDSC) in human colorectal carcinoma (CRC).

Methods: Samples of peripheral blood and tumor tissue from 49 CRC patients were analyzed. Mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation and were subjected to a flow cytometry-based immunophenotypic analysis.

Results: A considerable increase in the percentage of CD33⁺HLA-DR⁻ MDSCs was observed in the peripheral blood (1.89% ± 0.75%) and tumor tissues (2.99% ± 1.29%) of CRC patients as compared with that in the peripheral blood of healthy controls (0.54% ± 0.35%). This expanded CD33⁺HLA-DR⁻ subset exhibited immature myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Further studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis(P = 0.023), whereas that in tumor tissues was correlated with nodal/distant metastasis (P = 0.016/P = 0.047) and tumor stage (P = 0.028), suggesting the involvement of MDSCs in CRC tumor development.

Conclusion: Characterization of MDSCs in CRC suggests the clinical significance of circulating and tumor-infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs.

Keywords: Colorectal carcinoma; Myeloid-derived suppressor cell; Tumor metastasis.

MeSH terms

  • Biomarkers, Tumor / analysis
  • CD11b Antigen / analysis
  • CD18 Antigens / analysis
  • Carcinoma / immunology*
  • Carcinoma / secondary
  • Case-Control Studies
  • Cell Separation / methods
  • Centrifugation, Density Gradient
  • Chi-Square Distribution
  • China
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Female
  • Flow Cytometry
  • HLA-DR Antigens / analysis
  • Humans
  • Immunophenotyping
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Myeloid Cells / immunology*
  • Neoplasm Staging
  • Phenotype
  • Sialic Acid Binding Ig-like Lectin 3 / analysis
  • Tumor Escape*

Substances

  • Biomarkers, Tumor
  • CD11b Antigen
  • CD18 Antigens
  • CD33 protein, human
  • HLA-DR Antigens
  • ITGAM protein, human
  • Sialic Acid Binding Ig-like Lectin 3