Reversal of myeloid cell-mediated immunosuppression in patients with metastatic renal cell carcinoma

Clin Cancer Res. 2008 Dec 15;14(24):8270-8. doi: 10.1158/1078-0432.CCR-08-0165.


Purpose: Tumor-induced immunosuppression remains a significant obstacle that limits the efficacy of biological therapy for renal cell carcinoma. Here we evaluate the role of CD33 myeloid-derived suppressor cells (MDSC) in the regulation of T-cell responses in renal cell carcinoma patients. We also examine effect of all-trans-retinoic acid (ATRA) on MDSC-mediated immune suppression.

Experimental design: CD33-positive myeloid cells were isolated from the peripheral blood of renal cell carcinoma patients with magnetic beads and tested in vitro for their ability to inhibit T-cell responses. T-cell function was evaluated using ELISPOT and CTL assays.

Results: MDSC isolated from renal cell carcinoma patients, but not from healthy donors, were capable of suppressing antigen-specific T-cell responses in vitro through the secretion of reactive oxygen species and nitric oxide upon interaction with CTL. MDSC-mediated immune suppression and IFN-gamma down-regulation was reversible in vitro by exposing cells to the reactive oxygen species inhibitors. Moreover, ATRA was capable of abrogating MDSC-mediated immunosuppression and improving T-cell function by direct differentiation into antigen-presenting cell precursors.

Conclusions: These results may have significant implications regarding the future design of active immunotherapy protocols that may include differentiation agents as part of a multimodal approach to renal cell carcinoma immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Carcinoma, Renal Cell / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • HLA-DR Antigens / analysis
  • Humans
  • Immune Tolerance*
  • Kidney Neoplasms / immunology*
  • Myeloid Cells / physiology*
  • Sialic Acid Binding Ig-like Lectin 3
  • Tretinoin / pharmacology


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD33 protein, human
  • HLA-DR Antigens
  • Sialic Acid Binding Ig-like Lectin 3
  • Tretinoin
  • Granulocyte-Macrophage Colony-Stimulating Factor