B7-H3 expression in colorectal cancer: associations with clinicopathological parameters and patient outcome

Ingebrigtsen, Vibeke Anett; Boye, Kjetil; Nesland, Jahn M.; Nesbakken, Arild; Flatmark, Kjersti; Fodstad, Øystein

doi:10.1186/1471-2407-14-602

Cited by 74 publications

(65 citation statements)

References 42 publications

(45 reference statements)

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“…B7-H3 expression has been overexpressed in various human cancers, and its expression level significantly associated with clinicopathological parameters and survival status of patients, as well as densities of infiltrating immune cell subsets, such as lung cancer [31], renal cancer [32], colorectal cancer [33], and acute leukemia [34]. However, the expression and prognostic role of B7-H3 in ESCC cohort is still unknown.…”

Section: Discussionmentioning

confidence: 97%

Roles of coinhibitory molecules B7-H3 and B7-H4 in esophageal squamous cell carcinoma

et al. 2015

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The coinhibitory molecules, B7-H3 and B7-H4, have shown negative regulation in T cell activation and tumor-associated macrophage (TAM) polarization in tumor-specific immunity. Here, we investigated the expression of B7-H3 and B7-H4 in human and murine esophageal squamous cell carcinoma (ESCC) tissues to define their clinical significance and mechanism in a tumor microenvironment. In the present study, B7-H3 and B7-H4 were expressed in 90.6 and 92.7 % samples, respectively. High B7-H3 and B7-H4 expression was associated with advanced TNM stage and lymph node metastasis (p < 0.05, respectively). Patients with both B7-H3 and B7-H4 high-expressed tumors had the poorest prognosis (26.7 months), whereas those with both low-expressed tumors had the best survival (56.7 months). B7-H3 and B7-H4 expression were inclined to be positively related to the infiltration intensity of Treg cells and TAMs (p < 0.05, respectively), and B7-H3 expression is negatively associated with the intensity of CD8(+) T cells (p < 0.05). In 4-nitroquinoline 1-oxide (4-NQO)-induced murine models, high B7-H3 expression could only be detected at carcinoma stage, but abnormal B7-H4 expression appeared a little earlier at dysplasia stage. In vitro studies revealed that knockdown of B7-H3 on tumor cells suppressed ESCC cell migration and invasion, while knockdown of B7-H4 could inhibit ESCC cell growth. Overall, B7-H3 and B7-H4 are involved in ESCC progression and development and their coexpression could be valuable prognostic indicators. Interference of these negative regulatory molecules might be a new strategy for treating ESCC.

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Section: Discussionmentioning

confidence: 97%

Roles of coinhibitory molecules B7-H3 and B7-H4 in esophageal squamous cell carcinoma

et al. 2015

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“…Overexpression of B7-H3 has been associated with multiple cancers including esophageal cancer [41], pancreatic cancer [26], cervical cancer [36], non-small-cell lung cancer [38] and colorectal cancer [37]. However, high B7-H3 expression is also reported to be associated with better survival in acute myeloid leukemia [23].…”

Section: Discussionmentioning

confidence: 99%

B7-H3 Overexpression Predicts Poor Survival of Cancer Patients: A Meta-Analysis

Zheng

et al. 2016

Cell Physiol Biochem

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Background: B7-H3 exhibits altered expression in various cancers. However, the correlation between B7-H3 expression and prognosis of cancer patients remains controversial. Therefore, we elicit a meta-analysis to investigate the potential value of B7-H3 in the prognostic prediction in human cancers. Materials and Methods: We searched PubMed (last update by June 15th, 2016) to identify studies assessing the effect of B7-H3 on survival of cancer patients. Hazard ratios (HRs) for overall survival (OS), recurrence free survival (RFS) and progression-free survival (PFS) from individual studies were calculated and pooled by using a random-effect or fix-effect model, and heterogeneity and publication bias analyses were also performed. Results: Data from 24 observational studies consisting of 4141 patients were summarized. An elevated baseline B7-H3 was significantly correlated with poor OS (pooled HR = 2.09; 95% CI =1.60-2.74; P < 0.001). Differences across subgroups of tumor type (P = 0.324), year of publication (P = 0.431), ethnicity (P = 0.940), source of HR (P = 0.145), analysis type (P = 0.178) and sample size (P = 0.909) were not significant. Furthermore, high B7-H3 expression also predicted a significantly poor RFS (pooled HR = 1.39; 95% CI = 1.11-1.75; P = 0.004) but not PFS. Conclusions: This meta-analysis clarifies that elevated B7-H3 expression is significantly associated with poor survival in cancer patients.

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“…Numerous studies have described B7-H3 overexpression in human malignancies, including melanoma (22), leukemia (23), breast (24), prostate (25), ovarian (26), pancreatic (27) colorectal (28) and other cancers. As detected by immunochemistry technique, over 60% and up to 93% of patient tumor tissues display aberrant expression of B7-H3 in the vast majority of cancer types ( Table 1 ), while limited expression is seen on normal healthy tissues.…”

Section: Introductionmentioning

confidence: 99%

Molecular Pathways: Targeting B7-H3 (CD276) for Human Cancer Immunotherapy

Picarda

Ohaegbulam

Zang

2016

Clinical Cancer Research

417

373

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B7-H3 (CD276) is an important immune checkpoint member of the B7 and CD28 families. Induced on antigen presenting cells, B7-H3 plays an important role in the inhibition of T cell function. Importantly, B7-H3 is highly overexpressed on a wide range of human solid cancers and often correlates with both negative prognosis and poor clinical outcome in patients. Challenges remain to identify the receptor(s) of B7-H3 and thus better elucidate the role of the B7-H3 pathway in immune responses and tumor evasion. With a preferential expression on tumor cells, B7-H3 is an attractive target for cancer immunotherapy. Based on the clinical success of inhibitory immune checkpoint blockade (CTLA-4, PD-1 and PD-L1), developing monoclonal antibodies (mAbs) against B7-H3 appears promising therapeutic strategies. An unconventional mAb against B7-H3 with antibody-dependent cell-mediated cytotoxicity is currently being evaluated in a Phase I clinical trial and has shown encouraging preliminary results. Additional therapeutic approaches in targeting B7-H3, such as blocking mAbs, bispecific mAbs, chimeric antigen receptor T cells, small molecules inhibitors, and combination therapies should be evaluated as these technologies have already shown positive results in various cancer settings. A better understanding of the B7-H3 pathway in humans will surely help to further optimize associated cancer immunotherapies.

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B7-H3 expression in colorectal cancer: associations with clinicopathological parameters and patient outcome

Cited by 74 publications

References 42 publications

Roles of coinhibitory molecules B7-H3 and B7-H4 in esophageal squamous cell carcinoma

Roles of coinhibitory molecules B7-H3 and B7-H4 in esophageal squamous cell carcinoma

B7-H3 Overexpression Predicts Poor Survival of Cancer Patients: A Meta-Analysis

Molecular Pathways: Targeting B7-H3 (CD276) for Human Cancer Immunotherapy

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