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

Abstract

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.

<p>B7-H3 Induces Ovarian Cancer Drugs Resistance Through An PI3K/AKT/BCL-2 Signaling Pathway</p>

“…Accumulating evidence indicates that B7-H3 is present abundantly in several tumor types and participates in the immunosuppression and tumor progressions. [19][20][21] In the present study, we observed restricted expression of B7-H3 in tumor tissues from low-malignant patients, but enriched expression in those ovarian tumor tissues from high-malignant patients. The expression of B7-H3 also induces the stem-like phenotypes and drugs resistance of ovarian cancer cells in vitro and vivo, which is consistent with precious reports in prostatic cancer and bladder cancer.…”

Expression of inhibitory checkpoint ligands by Glioblastoma Multiforme cells and the implications of an enhanced stem cell-like phenotype

“…B7-H3, the only commonly elevated ligand by NZB11 and NZB19 gCSCs, expression correlates with glioma grade and negatively correlates with T-cell mediated immune response to glioma (41,42). While B7-H3 expression has not been well characterised on glioma cancer stem cell subsets beyond this study, the elevated expression here suggests to a mechanism by which B7-H3 expression on GBM cancer stem cells could drive worsening prognosis through enhanced immunological inhibition.…”

Identification of a prognostic immune signature for esophageal squamous cell carcinoma to predict survival and inflammatory landscapes

“…Therefore, we sought to examine the correlation between the risk score and immune checkpoints expression. We altogether enrolled 30 immune checkpoints in our analysis, including TNF superfamily (BTLA, TNFSF14, CD40, TNFRSF4, TNFRSF9, CD27, CD40LG, TNFSF4, TNFSF9, CD70 and TNFRSF18) [17], B7-CD28 family (CD274, PDCD1LG2, ICOSLG, CD276, VTCN1, HHLA2, CTLA4, ICOS, PDCD1, and TMIGD2) [18,19], and other immune checkpoint members (HAVCR2, IDO1, LAG3, FGL1, ENTPD1, NT5E, SIGLEC15, C10orf54 and NCR3) [20][21][22]. The heatmap for immune checkpoints expression was produced, taking other clinical characteristics into consideration, such as sex, age, TNM stage, and lymphatic metastasis (Fig.5B).…”