Circulating and tumor‐infiltrating myeloid cell subsets in patients with bladder cancer

Abstract

Both cancer-related inflammation and tumor-induced immune suppression are associated with expansion of myeloid cell subsets including myeloid-derived suppressor cells. However, little known regarding characteristics of myeloid cells in patients with bladder cancer. In this study, we analyzed myeloid cells from peripheral blood (PBMC) and tumor tissue that were collected from patients with superficial noninvasive and invasive urothelial carcinomas. Our results demonstrate that PBMC from bladder cancer patients contain two major CD11b myeloid cell subsets: granulocyte-type CD15 high CD33 low cells and monocyte-type CD15 low CD33 high cells. The number of circulating granulocytic but not monocytic myeloid cells in cancer patients was markedly increased when compared to healthy individuals. Both myeloid cell subsets from cancer patients were highly activated and produced substantial amounts of proinflammatory chemokines/cytokines including CCL2, CCL3, CCL4, G-CSF, IL-8 and IL-6. Granulocytic myeloid cells were able to inhibit in vitro T cell proliferation through induction of CD4 1 Foxp3 1 T regulatory cells. Analysis of bladder cancer tissues revealed that tumors were infiltrated with monocyte-macrophage CD11b 1 HLA-DR 1 and granulocytic CD11b 1 CD15 1 HLA-DR -myeloid cells. Collectively, this study identifies myeloid cell subsets in patients with bladder cancer. We demonstrate that these highly activated inflammatory myeloid cells represent a source of multiple chemokines/cytokines and may contribute to inflammation and immune dysfunction in bladder cancer.

Monocytic myeloid-derived suppressor cells as a potent suppressor of tumor immunity in non-small cell lung cancer

“…The presence of IL-10 has been confirmed in various types of cancer, including B-cell non-Hodgkin lymphoma (NHL), prostate cancer, melanoma, squamous cell carcinoma of the head and neck, hepatocellular carcinoma, multiple myeloma, glioblastoma and bladder carcinoma (5,(38)(39)(40). According to Feng et al (32), IL-10 is responsible for upregulating arginase 1 and therefore inhibits T-cell activation in patients with NSCLC.…”

Myeloid-Derived Suppressor Cells Predict Survival of Patients with Advanced Melanoma: Comparison with Regulatory T Cells and NY-ESO-1- or Melan-A–Specific T Cells

“…Various populations of MDSCs with several distinct phenotypes have been described over the last years, with a shared common suppressive function on adaptive and innate immunity (12,13). Circulating MDSCs have been shown to correlate with grading, stage, and tumor burden (14)(15)(16)(17) or with clinical outcome in patients with different types of cancer (18)(19)(20). At present, there are conflicting data on the prognostic significance of circulating MDSCs in melanoma (6,21,22).…”

COX2/mPGES1/PGE 2 pathway regulates PD-L1 expression in tumor-associated macrophages and myeloid-derived suppressor cells

“…This fact may suggest that PD-L1 can be induced in tumor vicinity via interaction with tumor-recruited inflammatory cells frequently presented in cancer tissues. Bladder cancer, in particularly, is characterized by the marked infiltration with immune and inflammatory cells such as macrophages and myeloid-derived suppressor cells (MDSCs) of bone marrow (BM) origin (6)(7)(8)(9). Peripheral blood in cancer patients, including those with bladder cancer, also comprises high numbers of myeloid cells, indirectly indicating that tumors may recruit BM-derived cells to support tumor growth through multiple mechanisms including local immunosuppression in tumor site (10,11).…”