Cancer cell‑expressed B7‑H3 regulates the differentiation of tumor‑associated macrophages in human colorectal carcinoma

Mao, Yong; Chen, Lüjun; Wang, Fengming; Zhu, Dawei; Ge, Xiaosong; Hua, Dong; Sun, Jing

doi:10.3892/ol.2017.6935

Cited by 52 publications

(59 citation statements)

References 30 publications

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“…In addition, we found that there was a significant correlation between B7-H3 and CD68 expression. This result is consistent with our previous findings (24), and our group also found that B7-H3 regulates the differentiation of tumor-associated macrophages in human colorectal carcinoma (43). However, the correlation between B7-H3 and CD31 or α-SMA expression was much higher than that of B7-H3 and CD68 expression, suggesting that B7-H3 may play a vital role in the tumor microenvironment, including endothelial cells and fibroblasts.…”

Section: Discussionsupporting

confidence: 92%

Overexpression of B7-H3 in α-SMA-Positive Fibroblasts Is Associated With Cancer Progression and Survival in Gastric Adenocarcinomas

et al. 2020

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Background: B7-H3 promotes tumor immune escape and is highly expressed in tumor tissues. Stromal cells in tumors, including fibroblasts, play an important role in this process; however, the role of B7-H3 in tumor fibroblasts has not been fully clarified. Methods: We examined B7-H3, CD31, and alpha-smooth muscle actin (α-SMA) protein expression in 268 gastric adenocarcinomas (GACs) by immunohistochemistry. The coexpression of B7-H3 with CD31 or α-SMA was examined using immunofluorescence double staining. Cytokine expression from fibroblasts treated with B7-H3 small interfering RNA (siRNA) was analyzed by a Quantitative reverse transcription-polymerase chain reaction (qPCR) and Enzyme-linked immunosorbent assay (ELISA). The transwell tests were conducted to assess the migration and invasion ability of fibroblasts. The overall survival was analyzed by a Kaplan-Meier analysis. Associations between categorical variables were assessed using the Pearson's Chi-square test or Fisher's exact test. Results: GAC patients with B7-H3 expression showed significantly poorer survival (P = 0.012). The overall survival of the group with high B7-H3 expression was significantly worse than the group with low B7-H3 expression in both tumor cells and in stromal cells (P = 0.007 and P = 0.048, respectively). B7-H3 expression correlated with many clinicopathological data, including tumor stage, tumor depth, lymph node involvement, and survival. Immunofluorescence staining showed that B7-H3 was expressed in tumor cells and α-SMA-positive fibroblasts. Remarkably, high expression of α-SMA was associated with a poor prognosis (P = 0.007), and the prognoses of patients with high stromal expression of B7-H3 and α-SMA were significantly worse than that of other combination types (P = 0.001). Additionally, the absence of B7-H3 led to decreased secretion of cytokines, such as interleukin (IL)-6 and vascular endothelial growth factor (VEGF), as well as a decline in migration and invasion ability in cancer-associated fibroblasts (CAFs). Zhan et al. B7-H3 Highly Expressed in CAFS Conclusions: Patients with high B7-H3 expression either in tumor cells or in stromal cells had significantly poorer overall survival. Stromal B7-H3 expression was mostly detected in α-SMA-positive CAFs. GAC patients with both stromal B7-H3-high and α-SMA-high expression had significantly poorer overall survival, suggesting that stromal B7-H3 and α-SMA expression status can serve as an indicator of poor prognosis for GAC patients.

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Section: Discussionsupporting

confidence: 92%

Overexpression of B7-H3 in α-SMA-Positive Fibroblasts Is Associated With Cancer Progression and Survival in Gastric Adenocarcinomas

et al. 2020

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“…In colorectal carcinoma (CRC) tissues, expression of B7-H3 and infiltrating macrophage density were found to be positively associated, while both were negatively correlated with patients' survival rate. Since the presumed receptor of B7-H3 was found on activated monocytes and macrophages, these results further indicated the potential role of B7-H3 signal and macrophages in tumor progression [13]. High B7-H3 expression was found in human breast cancer tissues and may play an important role in tumor progression and invasiveness.…”

Section: Roles Of B7-h3 In Tumor Progression and Drug Resistancementioning

confidence: 58%

“…B7-H3 was found to be overexpressed among several kinds of human cancer cells and was correlated with disease deteriorations [13][14][15][16][17][18][19] (Table 2). B7-H3 was recognized as a co-stimulatory molecule for immune reactions such as T cell activation and IFN-γ production [20].…”

Section: Biological Function Of B7-h3mentioning

confidence: 99%

B7-H3, a checkpoint molecule, as a target for cancer immunotherapy

2020

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B7-H3 (also known as CD276) is a newly found molecule of B7 family, which may be a promising target for cancer treatment. B7-H3 protein was demonstrated to be expressed in several kinds of tumor tissues including non-small-cell lung cancer (NSCLC) and prostate cancer. Its expression is highly associated with undesirable treatment outcomes and survival time, due to function of the immune checkpoint molecule. It was classified as either a co-stimulatory molecule for T cell activation or the nonimmunological role of regulating signaling pathways. Although there is still no agreed conclusion on the function of B7-H3, it may be a valuable target for cancer therapy. This review aims to provide a comprehensive, up-to-date summary of the advances in B7-H3 targeting approaches in cancer therapy. Although several challenges remain, B7-H3 offers a new therapeutic target with increased efficacy and less toxicity in future cancer treatment.

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“…Hence, the function of B7-H3 in glioma may realized by the wide expression of B7-H3 in glioma cells and endothelial cells. Additionally, up-regulation of B7-H3 expression in macrophages has been reported in several cancers, 31,32 but the expression panel of B7-H3 in glioma associated macrophage is unknown. Here, for the first time, we showed that B7-H3 expression was significantly up-regulated in GBM infiltrating macrophages, indicating that B7-H3 may act as a potent adjunct to facilitating the immune evasion function of macrophages.…”

Section: Discussionmentioning

confidence: 99%

Large-scale analysis reveals the specific clinical and immune features of B7-H3 in glioma

Zhang

et al. 2018

OncoImmunology

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Background: B7-H3 is an immune checkpoint member that belongs to B7-CD28 families and plays a vital role in the inhibition of T-cell function. Importantly, B7-H3 is widely overexpressed on solid tumors, making it become an attractive target for cancer immunotherapy. To clarify the expression panel of B7-H3 in glioma, we explored the clinical and immune features of B7-H3 expression in a large-scale study. Methods and patients: Totally, 1323 glioma samples from Chinese Glioma Genome Atlas (CGGA) dataset, including 325 RNAseq data and 301 mRNA microarray data, and The Cancer Genome Atlas (TCGA) dataset, including 697 RNAseq data, were gathered into our research. The statistical analysis and graphical work were mainly realized by R language. Results: B7-H3 expression was found positively correlated with the grade of malignancy, which might be caused by hypomethylation. The expression level of B7-H3 was consistently up-regulated in IDH wild-type glioma and highly enriched in mesenchymal subtype. GSEA analysis suggested that B7-H3 related genes were more involved in immune response and angiogenesis in glioma. Moreover, B7-H3 showed a consistent positive relationship with stromal and immune cell populations. Further analysis confirmed that B7-H3 played an important role in T-cell-mediated immunity, especially in T-cell-mediated immune response to tumor cell. Circos plots revealed that B7-H3 was tightly associated with most B7 members and other immune checkpoints. Univariate and multivariate cox analysis demonstrated that B7-H3 was an independent prognosticator for glioma patients. Conclusion: B7-H3 represents the malignant phenotype of glioma and independently predicted worse prognosis in glioma patients. Moreover, B7-H3 collaborating with other checkpoint members may contribute to the dysfunctional phenotype of T cell. These findings will be helpful for further optimizing immunotherapies for glioma.

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Cancer cell‑expressed B7‑H3 regulates the differentiation of tumor‑associated macrophages in human colorectal carcinoma

Cited by 52 publications

References 30 publications

Overexpression of B7-H3 in α-SMA-Positive Fibroblasts Is Associated With Cancer Progression and Survival in Gastric Adenocarcinomas

Overexpression of B7-H3 in α-SMA-Positive Fibroblasts Is Associated With Cancer Progression and Survival in Gastric Adenocarcinomas

B7-H3, a checkpoint molecule, as a target for cancer immunotherapy

Large-scale analysis reveals the specific clinical and immune features of B7-H3 in glioma

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