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

被引:162
作者
Eruslanov, Evgeniy
Neuberger, Molly
Daurkin, Irina
Perrin, George Q.
Algood, Chester
Dahm, Philipp
Rosser, Charles [2 ]
Vieweg, Johannes
Gilbert, Scott M.
Kusmartsev, Sergei [1 ,3 ]
机构
[1] Univ Florida, Canc & Genet Res Ctr, Coll Med, Dept Urol, Gainesville, FL 32610 USA
[2] MD Anderson Canc Ctr Orlando, Canc Res Inst, Orlando, FL 32827 USA
[3] Univ Florida, Dept Anat & Cell Biol, Gainesville, FL 32610 USA
关键词
bladder cancer; myeloid cells; inflammation; immune suppresision; chemokines; tumor-infiltrating myeloid cells; SUPPRESSOR-CELLS; 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE; ACTIVATED GRANULOCYTES; IMMUNE SUPPRESSION; OXIDATIVE STRESS; EXPRESSION; MECHANISM; CARCINOMA; IMMUNOSUPPRESSION; INFLAMMATION;
D O I
10.1002/ijc.26123
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 CD15high CD33low cells and monocyte-type CD15low CD33high 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+Foxp3+ T regulatory cells. Analysis of bladder cancer tissues revealed that tumors were infiltrated with monocytemacrophage CD11b+HLA-DR+ and granulocytic CD11b+CD15+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.
引用
收藏
页码:1109 / 1119
页数:11
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