Disease relevance of CD274

• RESULTS: B7h and B7-H1 messenger RNA was detected in IEC lines and IECs from healthy controls and patients with inflammatory bowel disease (IBD) [1].
• Human rhinoviruses inhibit the accessory function of dendritic cells by inducing sialoadhesin and B7-H1 expression [2].
• CONCLUSIONS: The expression of B7-H1 on tumor cells in local areas reciprocally correlated with the number of TILs, and this may contribute to negative regulation in antitumor immune responses in non-small cell lung cancer [3].
• Expression of Costimulatory Molecules on Human Retinoblastoma Cells Y-79: Functional Expression of CD40 and B7H1 [4].
• These results suggest that epithelial B7-H1 and B7-DC play a role in virus-associated immune responses in the airways [5].
• Blockade of B7-H1 signaling could improve hepatitis B c Ag-pulsed monocyte-derived DC-induced IFN-gamma production by autologous hepatitis B virus-specific T cells [6].
• The PD-1/PD-L pathway can be a good target for restoring antitumor immunity in ovarian cancer [7].
• PD-L1 may thwart effective antitumor immune responses and represents an attractive target for lymphoma immunotherapy [8].
• AP-1 signaling and EBV infection represent alternative mechanisms of PD-L1 induction and extend the spectrum of tumors in which to consider PD-1 blockade [9].
• T-cell-infiltrated melanomas, particularly those with high CD8 T-cell content, are more likely to be associated with PD-L1 expression in tumor cells, an improved prognosis, and increased time to development of brain metastases [10].

High impact information on CD274

• Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma [11].
• Ligation of B7-H1 co-stimulated T-cell responses to polyclonal stimuli and allogeneic antigens, and preferentially stimulated the production of interleukin-10 [12].
• Interleukin-2, although produced in small amounts, was required for the effect of B7-H1 co-stimulation [12].
• B7h interacts with inducible costimulator (ICOS) on T cells and provides a positive signal, whereas B7-H1 and B7-DC interact with PD-1 and transmit an inhibitory signal [1].
• The expression and function of costimulatory molecules B7H and B7-H1 on colonic epithelial cells [1].

Chemical compound and disease context of CD274

• X-Ray-induced chromosomal aberrations (CA) were potentiated by post-treatments in G2 with either caffeine (caff) or poly-D-lysine (PDL) in root-tip cells of Allium cepa [13].
• B7-H1 glycoprotein blockade: a novel strategy to enhance immunotherapy in patients with renal cell carcinoma [14].

Biological context of CD274

• Most importantly, blocking of B7-H1 and Sn on R-DC with specific mAbs against both receptors reverted the inhibitory phenotype [2].
• Expression of B7-H1 protein was low in first-trimester placenta compared to second- and third-trimester tissue (P < 0.05) and was enhanced in cultured cytotrophoblasts by treatment with either interferon-gamma or epidermal growth factor (P < 0.05), suggesting that one or both of these mediators regulates B7-H1 expression in the placenta [15].
• The effect of transduced B7H1-EC was more apparent when the EC were fixed prior to coculture, a manipulation that reduces the strength of costimulation and prevents upregulation of the endogenous B7-H1 molecule [16].
• Aberrant antigen presentation by antigen-presenting cells (APCs) that exhibit increased B7-H1 expression and IL-10 production in HIV infection could be responsible for T-lymphocyte unresponsiveness and loss of protective immunity [17].
• Western blot analysis showed that B7-H1 expression was induced by various H. pylori strains and was independent of H. pylori virulence factors such as Cag, VacA, and Urease [18].

Anatomical context of CD274

• Furthermore, we examined the correlation between B7-H1 expression on tumor cells and the number of tumor-infiltrating lymphocytes (TILs) or PD-1 expression on TILs [3].
• RESULTS: Significant B7-H1 expression levels on leukemia cells were detected in 17 of 30 patients and in eight of nine cell lines [19].
• Immunohistochemistry demonstrated that B7-H1 is constitutively expressed by the syncytiotrophoblast and by extravillous cytotrophoblasts, both of which are juxtaposed to maternal blood and tissue [15].
• In contrast to B7-H1, B7-2 mRNA and protein were absent in cytotrophoblast cells but present in maternal macrophages and some fetal macrophages [15].
• These studies document expression of the B7 family proteins at the maternal-fetal interface and demonstrate that B7-H1 is positioned such that it could facilitate protection of fetal cells against activated maternal leukocytes [15].

Associations of CD274 with chemical compounds

• B7-H1 and B7-DC were constitutively expressed on the cells, and their expression was profoundly upregulated by stimulation with an analog of viral dsRNA, polyinosinic-polycytidylic acid [5].
• A relatively high concentration of dexamethasone (1 microM) was required to suppress the upregulation of B7-H1 or B7-DC [5].
• Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation [20].
• High-level expression of B7-H1 molecules by dendritic cells suppresses the function of activated T cells and desensitizes allergen-primed animals [21].
• Fluticasone treatment (10(-7) M) reduced the baseline expression and inhibited the induction of B7-H1 and B7-DC in BEAS2B cells [22].

Physical interactions of CD274

• Furthermore, the soluble PD-1 with high purity possessed specific binding activity with its cognate ligand PD-L1, and the dissociation constant was 0.43 nmol/L as determined by Scatchard plot analysis [23].

Regulatory relationships of CD274

• The costimulatory effect of B7H1-expressing IFN-gamma-treated Y-79 cells on proliferation of purified T cells was studied in Y-79/T-cell coculture experiments with a blocking anti-B7H1 monoclonal antibody (mAb) [4].
• In contrast, expression of inhibitory B7-H1 molecules was up-regulated and R-DC de novo expressed sialoadhesin (Sn) [2].
• ICOS-B7H interaction induces the production of IL-10 which inhibits the antitumor immune responses [24].
• Importantly, B7-H1 expressed on APC strongly inhibits autologous CD4 T-cell activation [25].
• Accordingly, protein expression of B7-H1 on monocytes was up-regulated after 24 h of IFN-beta application [25].

Other interactions of CD274

• In contrast, the expression of B7H1 on IFN-gamma-treated Y-79 cells contributes to the suppression of T cells [4].
• Functional relevance of B7-H1 for tumor-immune interactions was assessed by coculture experiments using purified, alloreactive CD4 and CD8 T cells in the presence of a neutralizing anti-B7-H1 antibody [19].
• Furthermore, in the presence of neutralizing B7-H1 antibody (mAb 5H1) occurred no significant changes in T cell IFN-gamma or IL-2 production or proliferation [19].
• Expression of B7-H1 and B7-DC on the airway epithelium is enhanced by double-stranded RNA [5].
• B7-H1 reduced secretion of IL-2 and IL-10 by memory T cells [16].
• Blocking the MEK/ERK pathway inhibited IFN-gamma-mediated and TLR-mediated expression of B7-H1 [26].

Analytical, diagnostic and therapeutic context of CD274

• The functional role of B7h and B7-H1 in the interaction between IECs and T cells was assessed in coculture experiments using purified anti-B7h or B7-H1 monoclonal antibodies (mAbs), B7h immunoglobulin (Ig), or B7-H1 fusion proteins [1].
• Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that B7-H1 mRNA is abundant in term placenta and that cytotrophoblasts are sources of this message [15].
• PATIENTS AND METHODS: Leukemia cells from 30 patients and 9 human leukemia cell lines were investigated for B7-H1 expression by flow cytometry [19].
• CONCLUSIONS: These data suggest that PD-L1 and PD-L2 status may be a new predictor of prognosis for patients with esophageal cancer and provide the rationale for developing novel immunotherapy of targeting PD-1/PD-L pathway [27].
• EXPERIMENTAL DESIGN: PD-L1 and PD-L2 gene expression was evaluated in 41 esophagectomy patients by real-time quantitative PCR [27].

References