Expression and Clinical Significance of Immune Checkpoint Regulator B7-H3 (CD276) in Human Meningioma

Deng

et al. 2020

J Immunother Cancer

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BackgroundCraniopharyngioma (CP) is a common refractory tumor of the central nervous system. However, little is known about the expression and clinical significance of B7 family ligands/receptors in CP patients. Thus, we conducted the present study to address this issue in a cohort of 132 CP cases.MethodsWe mapped and quantified the expression of B7 family ligands/receptors molecules programmed cell death ligand 1 (PD-L1), B7-H3, B7-H4 and V-domain Ig-containing suppressor of T cell activation (VISTA) in 89 adamantinomatous-type CP and 43 papillary-type CP samples using immunohistochemistry and immunofluorescence. Associations between the marker levels, clinicopathological variables and survival were evaluated.ResultsThe positive rates of PD-L1, B7-H3, B7-H4 and VISTA in the cohort of 132 CP cases were 76.5%, 100%, 40.2% and 80.3%, respectively. The cut-off values of PD-L1, B7-H3, B7-H4 and PD-L1 expression were determined by survival receiver operating characteristic (ROC) package, which was 70, 182, 0 and 20, respectively. Elevated expressions of PD-L1, B7-H3, B7-H4 and VISTA were significantly associated with some clinicopathological characteristics. Kaplan-Meier analysis indicated that higher VISTA expressions correlated with better overall survival (OS) and progression-free survival (PFS) (p=0.0053 and p=0.0066, respectively). Multivariate Cox regression analysis indicated that VISTA was an independent prognostic factor for OS (p=0.018) but not for PFS (p=0.898).ConclusionsWe found variable expression of PD-L1, B7-H3, B7-H4 and VISTA proteins in CPs. The results suggest that the expression level of VISTA may be used as an important indicator to predict the OS and PFS of CPs. B7 family ligands/receptors could be potential immunotherapeutic targets when treating CPs.

Section: Methodsmentioning

confidence: 99%

Expression and clinical significance of PD-L1, B7-H3, B7-H4 and VISTA in craniopharyngioma

Deng

et al. 2020

J Immunother Cancer

Self Cite

“…A previous study showed that all 16/21 meningioma specimens presented high B7-H3 expression with strong membrane staining in almost 100% of tumor cells and that B7-H3 expression in the five remaining meningioma tissues was moderate to high ( 26 ). B7-H3 expression was detected in 75%–90% of the tumor tissues in six out of eight cases, and extremely low levels of B7-H3 were detected in normal brain tissues ( 27 ). Wang et al.…”

Section: B7-h3 Is Highly Expressed In Different Types Of Human Cancersmentioning

confidence: 98%

B7-H3/CD276: An Emerging Cancer Immunotherapy

2021

Immunotherapy aiming at suppressing tumor development by relying on modifying or strengthening the immune system prevails among cancer treatments and points out a new direction for cancer therapy. B7 homolog 3 protein (B7-H3, also known as CD276), a newly identified immunoregulatory protein member of the B7 family, is an attractive and promising target for cancer immunotherapy because it is overexpressed in tumor tissues while showing limited expression in normal tissues and participating in tumor microenvironment (TME) shaping and development. Thus far, numerous B7-H3-based immunotherapy strategies have demonstrated potent antitumor activity and acceptable safety profiles in preclinical models. Herein, we present the expression and biological function of B7-H3 in distinct cancer and normal cells, as well as B7-H3-mediated signal pathways in cancer cells and B7-H3-based tumor immunotherapy strategies. This review provides a comprehensive overview that encompasses B7-H3’s role in TME to its potential as a target in cancer immunotherapy.

“…Several recent studies have aimed to characterize the interactions between meningiomas and the immune system. Specifically, studies of the immune microenvironment in meningiomas have revealed that checkpoint molecules like NY-ESO-1, PD-L1, PD-L2, B7-H3, and CTLA-4 are expressed in meningiomas and may be at least partly responsible for the suppression of the anti-tumor immune response ( 43 , 78 – 81 ). Programmed Death Ligand-1 (PD-L1) is expressed in meningiomas, and expression levels are higher for higher-grade tumors ( 80 ).…”

Section: Immunotherapeutic Strategies For High Grade Meningiomasmentioning

confidence: 99%

Basis for Immunotherapy for Treatment of Meningiomas

et al. 2020

Meningiomas are common tumors that account for approximately one third of CNS tumors diagnosed every year. They are classified by the World Health Organization in grades I-III. Higher grades have an increased rate of growth, invasiveness, rate of recurrence, and worse outcomes than lower grades. Most meningiomas are grade I, while ~18% of meningiomas are grade II and III in hospital-based series. Meningiomas are typically “benign” tumors that are treated with surgery and radiation. However, when they recur or are unresectable, treatment options are very limited, especially since they are chemotherapy-resistant. Recent advances in the treatment of cancers with immunotherapy have focused on checkpoint blockade as well as other types of immunotherapy. There is emerging evidence supporting the use of immunotherapy as a potentially effective treatment strategy for meningioma patients. The immune microenvironment of meningiomas is a complex interplay of genetic alterations, immunomodulatory protein expression, and tumor-immune cell interactions. Meningiomas are known to be infiltrated by immune cells including microglia, macrophages, B-cells, and T-cells. Several mechanisms contribute to decreased an ti-tumor immune response, allowing tumor growth and evasion of the immune system. We discuss the most current knowledge on the immune micro-environment of meningiomas, preclinical findings of immunotherapy in meningiomas, meningioma immunotherapy clinical trials, and also offer insight into future prospects for immunotherapies in meningiomas.