Cancer Immunology, Immunotherapy

, Volume 61, Issue 6, pp 827–838

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

  • I. Poschke
  • Y. Mao
  • L. Adamson
  • F. Salazar-Onfray
  • G. Masucci
  • R. Kiessling
Original article

DOI: 10.1007/s00262-011-1143-y

Cite this article as:
Poschke, I., Mao, Y., Adamson, L. et al. Cancer Immunol Immunother (2012) 61: 827. doi:10.1007/s00262-011-1143-y

Abstract

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.

Keywords

MDSC Dendritic cells Melanoma Vaccination Cancer 

Supplementary material

262_2011_1143_MOESM1_ESM.pdf (149 kb)
Supplementary material 1 (PDF 149 kb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • I. Poschke
    • 1
  • Y. Mao
    • 1
  • L. Adamson
    • 1
  • F. Salazar-Onfray
    • 2
  • G. Masucci
    • 1
  • R. Kiessling
    • 1
  1. 1.Department of Oncology and PathologyCancer Center Karolinska (R8:01), Karolinska InstitutetStockholmSweden
  2. 2.Millennium Institute on Immunology and Immunotherapy, Faculty of MedicineInstitute of Biomedical Sciences, University of ChileSantiagoChile

Personalised recommendations