Suppressor myeloid cells producing high levels of arginase are found in the tumors and spleen of mice with lung or colon cancer. These cells impair T cell proliferation and cytokine production. Blocking arginase in vivo induces an immune mediated anti-tumor response. The role of these cells in cancer patients is unknown. We studied 117 patients with metastatic cell carcinoma (RCC) prior to treatment and found a significantly increased arginase activity in the peripheral blood mononuclear cells (PBMC). These patients had a significantly decreased cytokine production and expressed low levels of the T cell receptor CD3ζ chain. To determine the source of arginase and its effect on T cells, cells were separated into different subsets. Arginase activity was limited to a specific subset of CD11b+, CD14- myeloid cells, but not in the CD11b+, CD14+ mature monocytes. The cells had the morphology of activated polymorphonuclear cells and expressed CD15. There was a statistical correlation between the number of arginase producing myeloid cells and the decreased levels of serum arginine and the diminished expression of CD3ζ chain in the patients. Depletion of the CD11b+, CD14- suppressor myeloid cells re-established T cell proliferation.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]