B7-H4 overexpression impairs the immune response of T cells in human cervical carcinomas

Wang, Xin; Wang, Tingting; Xu, Mingkai; Xiao, Ling; Luo, Yi; Wenlian, Huang; Zhang, Yan; Geng, Weipu

doi:10.1016/j.humimm.2014.10.002

Cited by 27 publications

(25 citation statements)

References 15 publications

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“…Additionally, tissues from breast, uterus, ovary, colon, and pancreas tumors showed a statistically significant increase in the percentage of cells expressing B7‐H4 . In the 4T1 metastatic breast cancer model, transfer of tumor cells into B7‐H4 −/− mice resulted in fewer lung nodules, enhanced survival, and decreased tumor infiltration of immunosuppressive cells, as compared to wildtype mice that received the 4T1 cells . Based on these findings expression of B7‐H4 within the tumor microenvironment, either by the tumor cells and/or by infiltrating monocytes is hypothesized to promote immune evasion.…”

Section: Functional Connection Between B7‐h4 and Tregsmentioning

confidence: 87%

Potential targeting of B7‐H4 for the treatment of cancer

Podojil

Miller

2017

Immunological Reviews

112

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Summary Observations noting the presence of white blood cell infiltrates within tumors date back more than a century, however the cellular and molecular mechanisms regulating tumor immunity continue to be elucidated. The recent successful use of monoclonal antibodies to block immune regulatory pathways to enhance tumor-specific immune responses for the treatment of cancer has encouraged the identification of additional immune regulatory receptor/ligand pathways. Over the past several years, a growing body of data has identified B7-H4 (VTCN1/B7x/B7S1) as a potential therapeutic target for the treatment of cancer. The potential clinical significance of B7-H4 is supported by the high levels of B7-H4 expression found in numerous tumor tissues and correlation of the level of expression on tumor cells with adverse clinical and pathologic features, including tumor aggressiveness. The biological activity of B7-H4 has been associated with decreased inflammatory CD4+ T-cell responses and a correlation between B7-H4-expressing tumor-associated macrophages and FoxP3+ regulatory T cells (Tregs) within the tumor microenvironment. Since B7-H4 is expressed on tumor cells and tumor-associated macrophages in various cancer types, therapeutic blockade of B7-H4 could favorably alter the tumor microenvironment allowing for antigen-specific clearance tumor cells. The present review highlights the therapeutic potential of targeting B7-H4.

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Section: Functional Connection Between B7‐h4 and Tregsmentioning

confidence: 87%

Potential targeting of B7‐H4 for the treatment of cancer

Podojil

Miller

2017

Immunological Reviews

112

View full text Add to dashboard Cite

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“…B7-H4 had a profound inhibitory effect on development and function of T cells [28]. Recent investigations also showed that B7-H4 overexpression could promote the proliferation of FOXP3+ regulatory T cells (Tregs) and the secretion of IL-10 and TGF-β1 [29]. B7-H4 was also found to be correlated with Tregs infiltration and thus facilitate the immune tolerance in tumor microenvironment [30].…”

Section: Discussionmentioning

confidence: 99%

Prognostic role of B7-H4 in patients with non-small cell lung cancer: A meta-analysis

Tan

Shen

2017

Oncotarget

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B7 homolog 4 (B7-H4) has been recently reported to be a prognostic marker in non-small cell lung cancer (NSCLC) in some studies. However, the results remained conflicting. Thus, we aimed to comprehensively assess the association between B7-H4 expression and prognosis of NSCLC patients by performing a meta-analysis. Relevant publications were thoroughly searched of PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI). The pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate the effects. A total of 9 studies comprising 1444 patients were included in this meta-analysis. B7-H4 overexpression was associated with presence of lymph node metastasis (OR=3.59, 95%CI=2.39-5.38, p<0.001; fixed effect), advanced TNM stage (OR=2.36, 95%CI=1.2-4.67, p=0.013; random effect), and poor differentiation (OR=2.11, 95%CI=1.12-3.99, p=0.021; fixed effect). However, B7-H4 had no significant correlation with gender, age or histology in NSCLC. Furthermore, in a fixed effects model, the results indicated that B7-H4 overexpression was significantly associated with poor OS (HR=2.03, 95%CI=1.41-2.92, p<0.001). This meta-analysis demonstrated that high B7-H4 expression is an unfavorable prognostic factor in NSCLC. Because few studies were included for meta-analysis and almost all included studies were performed on Chinese patients, therefore; large scale prospective studies are needed to verify our results.

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“…The aberrant expression of B7-H4 in tumor cells was also negatively correlated with CD8+ T cell density in the tumor stroma. B7-H4 knockdown increased CD8+ T cell–mediated cytotoxicity in vitro , suggesting that B7-H4 expression may shield tumors from immune surveillance by suppressing the tumor-infiltrating CD8+ T lymphocytes in the tumor microenvironment [23, 28]. B7-H4 overexpression in tumor was related to the increased immune escape.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases

et al. 2016

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Liver metastasis development in pancreatic cancer patients is common and confers a poor prognosis. Clinical relevance of biomarker analysis in metastatic tissue is necessary. B7-H4 has an inhibitory effect on T cell mediated response and may be involved in tumor development. Although B7-H4 expression has been detected in pancreatic cancer, its expression in liver metastases from pancreatic cancer is still unknown. In this study, overall 43 pancreatic cancer liver metastases (with matched primaries in 15/43 cases) and 57 pancreatic cancer cases without liver metastases or other distant metastases were analyzed for their expression of B7-H4 by immunohistochemistry. Survival curves and log-rank tests were used to test the association of B7-H4 expression with survival. B7-H4 was highly expressed in 28 (65.1%) of the 43 liver metastases and 9 (60.0%) of the 15 matched primary tumors. The expression of B7-H4 in liver metastases was significantly higher than in the matched primary tumors (p < 0.05). Patients with high B7-H4 expression in their primary pancreatic cancer had higher risk of developing liver metastases (p < 0.05). In univariate analysis, B7-H4 expression was significantly associated with the risk of death (p < 0.05). And the multivariate analysis identified that B7-H4 was an independent prognostic indicator (p < 0.05). Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis. B7-H4 may promote pancreatic cancer metastasis and was promising to be a potential prognostic indicator of pancreatic cancer.

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B7-H4 overexpression impairs the immune response of T cells in human cervical carcinomas

Cited by 27 publications

References 15 publications

Potential targeting of B7‐H4 for the treatment of cancer

Potential targeting of B7‐H4 for the treatment of cancer

Prognostic role of B7-H4 in patients with non-small cell lung cancer: A meta-analysis

Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases

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