Pten Null Prostate Epithelium Promotes Localized Myeloid-Derived Suppressor Cell Expansion and Immune Suppression during Tumor Initiation and Progression | |
Garcia, Alejandro J. ; Ruscetti, Marcus ; Arenzana, Teresita L. ; Tran, Linh M. ; Bianci-Frias, Daniella ; Sybert, Elysia ; Priceman, Saul J. ; Wu, Lily ; Nelson, Peter S. ; Smale, Stephen T. ; Wu, Hong | |
刊名 | molecular and cellular biology
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2014 | |
关键词 | COLONY-STIMULATING FACTOR BEARING MICE T-CELLS DENDRITIC CELLS SIPULEUCEL-T CROSS-TALK CANCER INFLAMMATION MACROPHAGE IMMUNOSUPPRESSION |
DOI | 10.1128/MCB.00090-14 |
英文摘要 | Chronic inflammation is known to be associated with prostate cancer development, but how epithelium-associated cancer-initiating events cross talk to inflammatory cells during prostate cancer initiation and progression is largely unknown. Using the Pten null murine prostate cancer model, we show an expansion of Gr-1(+) CD11b(+) myeloid-derived suppressor cells (MDSCs) occurring intraprostatically immediately following epithelium-specific Pten deletion without expansion in hematopoietic tissues. This MDSC expansion is accompanied by sustained immune suppression. Prostatic Gr-1(+) CD11b(+) cells, but not those isolated from the spleen of the same tumor-bearing mice, suppress T cell proliferation and express high levels of Arginase 1 and iNOS. Mechanistically, the loss of PTEN in the epithelium leads to a significant upregulation of genes within the inflammatory response and cytokine-cytokine receptor interaction pathways, including Csf1 and Il1b, two genes known to induce MDSC expansion and immunosuppressive activities. Treatment of Pten null mice with the selective CSF-1 receptor inhibitor GW2580 decreases MDSC infiltration and relieves the associated immunosuppressive phenotype. Our study indicates that epithelium-associated tumor-initiating events trigger the secretion of inflammatory cytokines and promote localized MDSC expansion and immune suppression, thereby promoting tumor progression.; Biochemistry & Molecular Biology; Cell Biology; SCI(E); 3; ARTICLE; hwu@mednet.ucla.edu; 11; 2017-2028; 34 |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://ir.pku.edu.cn/handle/20.500.11897/389426] ![]() |
专题 | 生命科学学院 |
推荐引用方式 GB/T 7714 | Garcia, Alejandro J.,Ruscetti, Marcus,Arenzana, Teresita L.,et al. Pten Null Prostate Epithelium Promotes Localized Myeloid-Derived Suppressor Cell Expansion and Immune Suppression during Tumor Initiation and Progression[J]. molecular and cellular biology,2014. |
APA | Garcia, Alejandro J..,Ruscetti, Marcus.,Arenzana, Teresita L..,Tran, Linh M..,Bianci-Frias, Daniella.,...&Wu, Hong.(2014).Pten Null Prostate Epithelium Promotes Localized Myeloid-Derived Suppressor Cell Expansion and Immune Suppression during Tumor Initiation and Progression.molecular and cellular biology. |
MLA | Garcia, Alejandro J.,et al."Pten Null Prostate Epithelium Promotes Localized Myeloid-Derived Suppressor Cell Expansion and Immune Suppression during Tumor Initiation and Progression".molecular and cellular biology (2014). |
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