B7-H1 Is Expressed by Human Endothelial Cells and Suppresses T Cell Cytokine Synthesis

Mazanet, Melissa M.; Hughes, Christopher C.W.

doi:10.4049/jimmunol.169.7.3581

Cited by 297 publications

(207 citation statements)

References 43 publications

Supporting

Mentioning

192

Contrasting

Unclassified

Order By: Relevance

“…The expression of PD-L1 on VECs has been related to the negative regulation of T cells. 17,18 In this study, we demonstrate that VECs not only express PD-L1, but also B7-1 (CD80), one of its receptors. The interaction between PD-1 and PD-L1 is well established as playing a vital role in controlling T-cell responses in a variety of contexts, from development to autoimmunity to microbial pathogenesis to tumor immunity.…”

Section: Discussionmentioning

confidence: 53%

“…15,16 Interestingly, PD-L1 also has been reported to be present on VECs under basal conditions, and the surface expression of PD-L1 on VECs can be increased by interferon-␣, -␤, and -␥. 17,18 However, the anti-angiogenic effect of PD-L1 has not been demonstrated to date. Here, we provide evidence for a novel regulatory function for PD-L1 in VEC proliferation in vitro and corneal angiogenesis in vivo.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Novel Function for Programmed Death Ligand-1

Jin

Chauhan

Annan

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Programmed death ligand-1 (PD-L1) plays a critical role in T-cell regulatory function. Here, we report a newly discovered effect of PD-L1 on angiogenesis. We demonstrate that PD-L1 and its receptor CD80, but not PD-1, are expressed by primary murine lung and heart vascular endothelial cells and the miscrovascular endothelial cell line (MS1) at both the mRNA and protein levels in vitro. The inhibition of PD-L1 or CD80 expression in MS1 cells, by small-interfering RNA transfection, led to a significant up-regulation of vascular endothelial growth factor receptor 2 expression and cell proliferation levels in MS1 cells. Furthermore, MS1 cells were found to have a significantly lower proliferation and vascular endothelial growth factor receptor 2 expression levels when they were co-cultured with PD-L1-expressing normal corneal epithelial cells, as compared to MS1 cells co-cultured with PD-L1 ؊/؊ corneal epithelial cells. In a sutureinduced corneal angiogenesis model, we observed a significantly higher level of angiogenic response in PD-L1 ؊/؊ knockout mice as compared to wild-type mice, although there was no significant difference in the expression of inflammatory cytokines (interleukin-1␣, interleukin-1␤, or tumor necrosis factor-␣) or the infiltration of innate immune cells (neutrophils and macrophages) between the two groups. We conclude that the expression of PD-L1 in both vascular endothelial cells and corneal epithelial cells regulates corneal angiogenesis.

show abstract

Section: Discussionmentioning

confidence: 53%

mentioning

confidence: 99%

A Novel Function for Programmed Death Ligand-1

Jin

Chauhan

Annan

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…In addition, B7-H1 was inducible in epidermal KC. Recent reports have suggested a regulatory function for B7-H1 expressed on normal tissue cells, such as endothelial cells [35] and trophoblasts [36,37]. Thus, it is possible that KC expressing B7-H1 may provide a regulatory function similar to that of APC at the local site.…”

Section: Discussionmentioning

confidence: 99%

Preferential contribution of B7‐H1 to programmed death‐1‐mediated regulation of hapten‐specific allergic inflammatory responses

et al. 2003

View full text Add to dashboard Cite

Programmed death-1 (PD-1) and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, are new CD28-B7 family members that may be involved in the regulation of immune responses. We examined the roles of these molecules in mouse hapten-induced contact hypersensitivity (CH). Administration of anti-PD-1 mAb at sensitization significantly enhanced and prolonged ear swelling. Treatment with anti-B7-H1 mAb, but not anti-B7-DC mAb, also enhanced CH reactions. The anti-PD-1 mAb treatment at sensitization significantly increased the T cell number of draining lymph nodes (DLN). B7-H1 was induced on activated T cells and antigen-presenting cells (APC) in the skin and the DLN, whereas B7-DC expression was restricted to dendritic cells (DC) in the dermis and the DLN. A particular subset of DC, B7-H1 + B7-DC -CD86 low , was found in sensitized DLN. The blockade of B7-H1, but not B7-DC, dramatically enhanced the initial T cell proliferative responses against hapten-pulsed DLN APC, suggesting the preferential contribution of B7-H1 to the T cell-APC interaction. Our results demonstrate the regulatory role of PD-1 and the differential roles of B7-H1 and B7-DC in hapten-induced immune responses. The PD-1-B7-H1 pathway may play a unique role in regulating inflammatory responses.

show abstract

“…The induction of B7-H1 molecule in the current primary cell lines is not dependent on inflammatory cytokines (g-IFN and TNF-a) known to induce B7-H1. [37][38][39] The similarity in the expression of B7-H1 in fibroblasts and epithelial cell cultures, obtained form either normal or tumor tissues, suggests that B7-H1 is directly related to proliferation and not tumorgenesis (cell transformation). Similarly, Parsa et al have recently found that expression of B7-H1 in human astrocytes was dependent on Akt activation but not on cellular immortalization or transformation.…”

Section: Discussionmentioning

confidence: 99%

Expression of B7‐H1 in breast cancer patients is strongly associated with high proliferative Ki‐67‐expressing tumor cells

Ghebeh¹,

Tulbah²,

Mohammed³

et al. 2007

Intl Journal of Cancer

132

106

View full text Add to dashboard Cite

B7-H1, a coinhibitory molecule, plays a role in immune escape of tumors. We have shown previously the expression of this molecule in breast cancer patients and demonstrated its association with high histological grade, progesterone and estrogen receptor negative status, all of which are known to have direct impact on cell proliferation. In the present work, we investigated the effect of proliferation, as measured by Ki-67 and mitotic count, on the induction of B7-H1. We used H&E stained sections to score for mitotic count in 69 breast cancer patients. Immunohistochemistry was used to investigate B7-H1 and Ki-67 expression. The relationship between B7-H1 induction and cell proliferation was further investigated in primary cultured cells. B7-H1 expression was recorded in patients with a high mitotic index (p 5 0.007). There was a high significant correlation between B7-H1 expression and the presence of the proliferative marker Ki-67 (p < 0.001) indicating the association of proliferation with B7-H1 induction. Furthermore, B7-H1 was gradually induced in proliferating cells of 8/8 primary cell lines as measured by Ki-67 expression. Finally, B7-H1 was downregulated in quiescent cells and upregulated in cells stimulated with a mitogen confirming the association of proliferation with the induction of B7-H1. We have shown for the first time a direct association between proliferation and the expression of B7-H1 in breast cancer patients. The relationship between B7-H1 induction and cell proliferation was also thoroughly investigated in vitro, in which a strong link between B7-H1 expression and the presence of the proliferative Ki-67 marker was clearly demonstrated. ' 2007 Wiley-Liss, Inc.Key words: B7-H1; PD-L1; breast cancer; Ki-67; proliferation; mitotic index About 40% of women still die of breast cancer in spite of the significant advances in traditional, targeted and neo-adjuvant therapies. 1 Immunotherapeutic strategies aimed at manipulating the patient's immune system to specifically destroy tumor cells may represent a major alternative approach for the management of cancer. 2,3 However, the presence of an existing immune tolerance in patients with advanced cancer may limit the clinical effectiveness of such therapeutic strategies. 4 Several mechanisms have been attributed to the immune defect seen in breast cancer patients with advanced disease; where a lower number of blood lymphocytes, 5 elevated T regulatory lymphocytes, 6 defective dendritic cells 7 and expression of FasL in breast cancer 8 were described.A T lymphocyte inhibitory molecule named B7-H1 (also called PD-L1) expressed by antigen presenting cells has been shown to induce T lymphocyte anergy and/or apoptosis after ligation to its T lymphocytes receptor PD-1. 9-12 It has been shown to be directly involved in the protection of cancer cells from activated T lymphocytes. 13 The expression of this molecule has been described in several malignancies including ovary, colon, melanoma and carcinoma of the lung. 11 Others includes; squamous cell carcinoma o...

show abstract

B7-H1 Is Expressed by Human Endothelial Cells and Suppresses T Cell Cytokine Synthesis

Cited by 297 publications

References 43 publications

A Novel Function for Programmed Death Ligand-1

A Novel Function for Programmed Death Ligand-1

Preferential contribution of B7‐H1 to programmed death‐1‐mediated regulation of hapten‐specific allergic inflammatory responses

Expression of B7‐H1 in breast cancer patients is strongly associated with high proliferative Ki‐67‐expressing tumor cells

Contact Info

Product

Resources

About