Pten Null Prostate Epithelium Promotes Localized Myeloid-Derived   Suppressor Cell Expansion and Immune Suppression during Tumor Initiation   and Progression

doi:10.1128/MCB.00090-14

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	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
	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).