Myeloid-derived suppressor cells impair the quality of dendritic cell vaccines

Cancer Immunol Immunother. 2012 Jun;61(6):827-38. doi: 10.1007/s00262-011-1143-y. Epub 2011 Nov 12.


Myeloid-derived suppressor cells (MDSC) are important regulators of the immune system and key players in tumor-induced suppression of T-cell responses. CD14+HLA-DR-/low MDSC have been detected in a great number of malignancies, including melanoma. MDSC are known to be impaired in their ability to differentiate along the myeloid lineage, e.g., into dendritic cells (DC). This is a concern for utilization of monocyte-derived DC for vaccination of patients with melanoma or other cancers exhibiting accumulation of CD14+ MDSC. When producing DC according to standard operating procedures of two currently ongoing clinical trials, we found that MDSC co-purified with monocytes isolated by elutriation. MDSC frequencies did not affect yield or viability of the produced DC, but induced a dose-dependent decrease in DC maturation, ability to take up antigen, migrate and induce T-cell IFNγ production. Changes in DC characteristics were most notable when 'pathological' frequencies of >50% CD14+HLA-DR- cells were present in the starting culture. The impaired DC quality could not be explained by altered cytokine production or increased oxidative stress in the cultures. Tracking of HLA-DR- cells throughout the culture period revealed that the observed changes were partially due to the impaired maturation and functionality of the originally HLA-DR- population, but also to their negative effects on HLA-DR+ cells. In conclusion, MDSC could be induced to differentiate into DC but, due to the impairment of overall DC vaccine quality when >50% HLA-DR- cells were present in the starting culture, their removal could be advisable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cancer Vaccines / immunology*
  • Coculture Techniques
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology*
  • Female
  • HLA-DR Antigens / immunology
  • Humans
  • Lipopolysaccharide Receptors / immunology
  • Male
  • Melanoma / immunology*
  • Melanoma / pathology
  • Melanoma / therapy
  • Middle Aged
  • Myeloid Cells / immunology*
  • Neoplasm Staging
  • Oxidative Stress / immunology


  • Cancer Vaccines
  • Cytokines
  • HLA-DR Antigens
  • Lipopolysaccharide Receptors