FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2488013324> ?p ?o ?g. }

• W2488013324 abstract "The tumor microenvironment contains a diverse population of myeloid cells that are recruited from bone marrow and converted to immunosuppressive cells, thus mediating tumor cell escape from immune checkpoint. We have identified a subset of dynamic bone marrow myeloid cells, which can be identified by histidine decarboxylase (Hdc) mRNA and GFP expression in Hdc-GFP transgenic mice. Gene expression profiling showed that Hdc-GFP+ CD11b+Gr1+ myeloid cells express higher levels of cell cycle promoting genes such as Ccnd2, Ccnd3 and Cdc14a, while cell proliferation repressors including Cdc14b, Cdc16 and Cdk4 were downregulated in Hdc-GFP+ myeloid cells.To further elucidate the role of Hdc+ myeloid cells in tumor progression, we performed lineage-tracing studies using Hdc-creERT2;R26-LSL-TdTomato reporter mice. Pulsed with tamoxifen, the majority of TdTomato+ cells were localized initially to a group of CD11b+Gr1+ myeloid cells representing the highest Hdc mRNA expression in bone marrow, spleen and blood. Later on, TdTomato+CD11b+Gr1- F4/80+ macrophages can be detected, indicating a hierarchy of Hdc+ myeloid cells in which Hdc+CD11b+Gr1+ myeloid cells reside at the apex. In general, CD11b+ myeloid cells have a relative short lifespan (<2 weeks); however, treatment with dextran sodium sulfate (DSS) in the drinking water increased the longevity and frequency of Hdc+ myeloid cells, also promoted the differentiation of Gr1+ immature myeloid cells into neutrophils and macrophages.In a mouse model of azoxymethane (AOM)/DSS colorectal carcinogenesis, Hdc-creERT2;R26-LSL-TdTomato;R26-LSL-DTA mice were injected with 10 mg/kg AOM and followed by 3 circles of 10 days 1.5% DSS ad libitum in drinking water. We found that Hdc-TdTomato labeled a proportion of tumor infiltrating CD11b+Gr1+ myeloid cells that expressed higher levels of Arg-1, Cox2, and Pdl1 transcripts. Continuous depletion of Hdc+ myeloid cells by administration of tamoxifen chow to induce DTA (diphtheria toxin subunit A) killing in Hdc-expressing myeloid cells abrogated half of the tumor-infiltrating MDSCs and released tumoricidal CD8+ T cells (> 15-fold), leading to decreased tumor number. This tumor suppression could be rescued by Hdc+ CD11b+Gr1+ cell adoptive transfer. Serum chemokine profiling revealed that Hdc+ DTA mediated myeloid depletion also decreased serum chemokine levels, among which Cxcl13 decreased the most (>30-fold). Cxcl13 protein and Cxcl13 mRNA also decreased in the colonic tumor tissue in the Hdc+ myeloid cell depleted AOM/DSS treatment group. Along with reduction in Cxcl13 levels, we also detected a significant reduction of Foxp3+ Treg cells in the tumor frozen sections stained with antibody against Foxp3 compared to R26-LSL-TdTomato;R26-LSL-DTA controls received the same treatments. Pre-knockdown of Cxcl13 by Dicer-substrate SiRNA (DsiRNAs) in a co-culture of splenic Hdc+ CD11b+Gr1+ myeloid cells from colon tumor-bearing mice with splenic Foxp3-GFP+ Treg cells induced apoptosis and decreased numbers of GFP+ cells compared to the scramble knockdown control group.Taken together, our data suggest that Hdc marks a distinct subset of myeloid cells with greater potency for promoting tumorigenicity, in part through supporting Tregs and suppressing CD8+ Tcells in the tumor microenvironment.Citation Format: Xiaowei Chen, Yoshihiro Takemoto, Karan K. Nagar, Timothy H. Chu, Zhengyu Jiang, Wenju Chang, Richard A. Friedman, Yagnesh H. Tailor, Daniel L. Worthley, Timothy C. Wang. Histidine decarboxylase (Hdc)-expressing myeloid cells support Foxp3+ Treg cells and promote colorectal cancer progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-272." @default.
• W2488013324 created "2016-08-23" @default.
• W2488013324 creator A5003427958 @default.
• W2488013324 creator A5008826006 @default.
• W2488013324 creator A5017702767 @default.
• W2488013324 creator A5020904079 @default.
• W2488013324 creator A5024794754 @default.
• W2488013324 creator A5034242696 @default.
• W2488013324 creator A5064812602 @default.
• W2488013324 creator A5065177568 @default.
• W2488013324 creator A5065277498 @default.
• W2488013324 creator A5087702334 @default.
• W2488013324 date "2016-07-15" @default.
• W2488013324 modified "2023-10-17" @default.
• W2488013324 title "Abstract LB-272: Histidine decarboxylase (Hdc)-expressing myeloid cells support Foxp3+ Treg cells and promote colorectal cancer progression" @default.
• W2488013324 doi "https://doi.org/10.1158/1538-7445.am2016-lb-272" @default.
• W2488013324 hasPublicationYear "2016" @default.
• W2488013324 type Work @default.
• W2488013324 sameAs 2488013324 @default.
• W2488013324 citedByCount "0" @default.
• W2488013324 crossrefType "proceedings-article" @default.
• W2488013324 hasAuthorship W2488013324A5003427958 @default.
• W2488013324 hasAuthorship W2488013324A5008826006 @default.
• W2488013324 hasAuthorship W2488013324A5017702767 @default.
• W2488013324 hasAuthorship W2488013324A5020904079 @default.
• W2488013324 hasAuthorship W2488013324A5024794754 @default.
• W2488013324 hasAuthorship W2488013324A5034242696 @default.
• W2488013324 hasAuthorship W2488013324A5064812602 @default.
• W2488013324 hasAuthorship W2488013324A5065177568 @default.
• W2488013324 hasAuthorship W2488013324A5065277498 @default.
• W2488013324 hasAuthorship W2488013324A5087702334 @default.
• W2488013324 hasConcept C203014093 @default.
• W2488013324 hasConcept C2779282312 @default.
• W2488013324 hasConcept C2780007613 @default.
• W2488013324 hasConcept C502942594 @default.
• W2488013324 hasConcept C86803240 @default.
• W2488013324 hasConceptScore W2488013324C203014093 @default.
• W2488013324 hasConceptScore W2488013324C2779282312 @default.
• W2488013324 hasConceptScore W2488013324C2780007613 @default.
• W2488013324 hasConceptScore W2488013324C502942594 @default.
• W2488013324 hasConceptScore W2488013324C86803240 @default.
• W2488013324 hasLocation W24880133241 @default.
• W2488013324 hasOpenAccess W2488013324 @default.
• W2488013324 hasPrimaryLocation W24880133241 @default.
• W2488013324 hasRelatedWork W178354296 @default.
• W2488013324 hasRelatedWork W1977841877 @default.
• W2488013324 hasRelatedWork W1982183191 @default.
• W2488013324 hasRelatedWork W2036233304 @default.
• W2488013324 hasRelatedWork W2038711570 @default.
• W2488013324 hasRelatedWork W2067160270 @default.
• W2488013324 hasRelatedWork W2093121249 @default.
• W2488013324 hasRelatedWork W2412318097 @default.
• W2488013324 hasRelatedWork W2587274998 @default.
• W2488013324 hasRelatedWork W3143809607 @default.
• W2488013324 isParatext "false" @default.
• W2488013324 isRetracted "false" @default.
• W2488013324 magId "2488013324" @default.
• W2488013324 workType "article" @default.