Prognostic role of high B7-H4 expression in patients with solid tumors: a meta-analysis

Song, Xing; Shao, Yingjie; Gu, Wenjing; Xu, Chao; Mao, Huihui; Pei, Honglei; Jiang, Jingting

doi:10.18632/oncotarget.8598

Cited by 19 publications

(19 citation statements)

References 43 publications

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“…Together these results demonstrate mutually exclusive expression of known negative regulators of T cells (such as PD-L1 or IDO1) which are positively correlated with presence of CD8 + T cells and the PD-L1 family member, B7-H4 which is negatively correlated with presence of CD8 + T cells. Our data thus reveals that expression of immune checkpoint targets is distinct between Although originally characterized by its expression on hematopoietic cells, elevated levels of B7-H4 on tumor cells, as was observed here, correlate with poor clinical outcome across multiple types of solid tumors (38). Consistent with our data, B7-H4 expression is upregulated by TGF-1 signaling in colorectal cancer (39).…”

Section: Discussionsupporting

confidence: 89%

Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers

Gruosso

Gigoux

Manem

et al. 2019

Journal of Clinical Investigation

319

302

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Understanding the tumor immune microenvironment (TIME) promises to be key for optimal cancer therapy, especially in triple-negative breast cancer (TNBC). Integrating spatial resolution of immune cells with laser capture microdissection gene expression profiles, we defined distinct TIME stratification in TNBC, with implications for current therapies including immune checkpoint blockade. TNBCs with an immunoreactive microenvironment exhibited tumoral infiltration of granzyme B + CD8 + T cells (GzmB + CD8 + T cells), a type 1 IFN signature, and elevated expression of multiple immune inhibitory molecules including indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand 1 (PD-L1), and resulted in good outcomes. An "immune-cold" microenvironment with an absence of tumoral CD8 + T cells was defined by elevated expression of the immunosuppressive marker B7-H4, signatures of fibrotic stroma, and poor outcomes. A distinct poor-outcome immunomodulatory microenvironment, hitherto poorly characterized, exhibited stromal restriction of CD8 + T cells, stromal expression of PD-L1, and enrichment for signatures of cholesterol biosynthesis. Metasignatures defining these TIME subtypes allowed us to stratify TNBCs, predict outcomes, and identify potential therapeutic targets for TNBC.

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Section: Discussionsupporting

confidence: 89%

Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers

Gruosso

Gigoux

Manem

et al. 2019

Journal of Clinical Investigation

319

302

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“…However, Zang et al [ 13 ] reported that B7-H4 wasn't an independent prognostic indicator, the reason why this phenomenon appeared may rely on the limited follow-up years for the long-survival period of prostate cancer patients. The previous meta-analysis which had investigated the high expression of B7-H4 influenced the prognosis of solid tumor patients also showed this trend as we illustrated [ 29 ]. While that article only included the samples derived from the tumor tissue and only contained 18 articles.…”

Section: Discussionsupporting

confidence: 73%

“…Compared with blocking the B7 family members which express precisely on various tumor, controlling the upstream stages in turn regulating effector T cells acting on peripheral tumors seems inefficient and imprecise [ 27 ]. B7-H1 is another potential immunotherapy target which is expressed on tumor and normal tissues, but B7-H4 can hardly be discovered in normal tissue and the expression pattern in tumor is wider than B7-H1[ 28 , 29 ]. Chen et al [ 30 ] also reported that B7-H4 overexpression was correlated with pancreatic cancer patients’ OS ( P < 0.001), whereas the expression of B7-H1 didn't ( p = 0.089).…”

Section: Discussionmentioning

confidence: 99%

“…Second, although our analysis contained more articles and supplied the studies with B7-H4 expressed in blood compared with the previous one, the number is still inadequate, and more studies are needed to be included to make the results more credible. Third, the data of several studies were extracted from survival curves, the statistical error was inevitable which could affect the precision of results and the differences could be observed compared with the former article [ 29 ]. Fourth, the detection methods and cut-off values were varied, and the inconformity of these items may result in the heterogeneity of overall results.…”

Section: Discussionmentioning

confidence: 99%

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B7-H4 as an independent prognostic indicator of cancer patients: a meta-analysis

et al. 2017

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The expression of B7-H4 was observed in a variety of tumors, however the prognostic value in cancer was still controversial. Therefore, we conducted this meta-analysis to explore the potential role of B7-H4 in cancer prognostic prediction. Twenty-seven studies including 3771 patients were brought into the analysis according to the inclusion and exclusion criteria. The pooled results demonstrated that elevated B7-H4 predicted a poor OS (HR = 1.93, 95% CI 1.71-2.18, P < 0.001) and DFS (HR = 1.84, 95% CI 1.46-2.33, P < 0.001). Subgroup analysis showed that races, tumor types, sample sources, analysis types, sources of HR and sample sizes exhibited non-significant distinctions with OS (PS = 0.878, PS = 0.143, PS = 0.613, PS = 0.639, PS = 0.48 and PS = 0.528, respectively). PubMed, Embase and the Cochrane Library were searched up to April 7, 2017, to recognize the available studies for assessing the association between B7-H4 and cancer patients’ outcome. We extracted the hazard ratio (HR), relative ratio (RR), odds ratio (OR) with their 95% confidence interval (CI) for overall survival (OS) or disease-free survival (DFS) as the effect size (ES) for the analysis. This meta-analysis demonstrates high expression of B7-H4 is a negative correlation with the outcome of cancer patients.

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“…The previous meta-analysis investigated whether high B7-H4 expression influenced the prognosis of solid tumor patients. [ 29 ] In our study, we found that high expression of B7-H4 was an independent prognostic indicator of poor survival. However, certain limitations to our study should be considered.…”

Section: Discussionmentioning

confidence: 57%

Does B7-H4 expression correlate with clinicopathologic characteristics and survival in ovarian cancer?

Wang²,

Li³

et al. 2018

Medicine

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Background:Several studies have shown that B7-H4 expression is significantly increased in ovarian cancer. However, the role of B7-H4 expression in ovarian cancer remains unclear, and some studies reporting conflicting results. A systematic review of the literature and meta-analysis were conducted to assess the clinicopathologic characteristics and prognostic significance of B7-H4 in ovarian cancer.Methods:Eligible studies were searched in the PubMed, MEDLINE, Cochrane Library, and the China National Knowledge Infrastructure databases. The included studies assessed the relationship between B7-H4 expression and clinicopathologic features or prognosis in patients with ovarian cancer through September 2017. A total of 1045 patients in 10 studies were included in the meta-analysis. Stata software version 12.0 was used to analyze the data. We used an odds ratio (OR) or hazard ratio (HR) with a 95% confidence interval (CI) to assess the risk or hazard association.Results:B7-H4 expression in ovarian cancer patients was significantly increased (OR: 4.20, 95% CI: 2.85–6.18, Z = 6.91, P < .05), and heterogeneity was low between studies (I2 = 8.2%, P = .366). With respect to the clinicopathologic features, no relation was detected between B7-H4 expression and International Federation of Gynaecology and Obstetricsstages stages (OR: 0.81, 95% CI: 0.64–1.03, Z = 1.70, P = .09), pathologic grade (OR: 0.91, 95% CI: 0.72–1.16, Z = 0.76, P = .45), tumor metastasis (OR: 1.25, 95% CI: 0.90–1.74, Z = 1.34, P = .18), or histologic type (OR: 1.17, 95% CI: 0.85–1.60, Z = 0.96, P = .34) in ovarian cancer. Furthermore, B7-H4 expression was significantly associated with a worse progression-free survival (PFS) (HR: 1.30, 95% CI: 1.17–1.45, Z = 4.79, P < .05).Conclusion:B7-H4 expression was related to ovarian cancer, but not to patients’ clinicopathologic characteristics. High B7-H4 expression was negatively correlated with survival outcome, suggesting that B7-H4 plays an essential role in poor prognosis in ovarian cancer patients.

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Prognostic role of high B7-H4 expression in patients with solid tumors: a meta-analysis

Cited by 19 publications

References 43 publications

Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers

Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers

B7-H4 as an independent prognostic indicator of cancer patients: a meta-analysis

Does B7-H4 expression correlate with clinicopathologic characteristics and survival in ovarian cancer?

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