B7-H1 Expression in Vestibular Schwannomas

Abstract

Hypothesis B7-H1 is expressed in vestibular schwannomas. Background Little is known about how benign human vestibular schwannomas interact with antibody-mediated or cell-mediated immunity. We report on the aberrant expression of a novel T-cell coregulatory molecule, B7 homolog 1 (B7-H1), in vestibular schwannomas and discuss the implications of B7-H1 expression and tumor aggressiveness and a potential regulator of B7-H1 expression. Methods Immunohistochemical staining for B7-H1, CD8+, CD3+, and CD4+ lymphocytes were performed on 48 fresh-frozen vestibular schwannoma tissue specimens. A clinical review of patient presenting symptoms and tumor characteristics was performed. Real-time polymerase chain reaction was used to determine if there was differential expression of B7-H1 messenger RNA and microRNA-513, a known regulator of B7-H1, in several strongly positive and negative B7-H1 vestibular schwannomas. Results Nine (19%) of 48 tumors were negative, 23 (48%) tumors were 1+ mildly positive (<20% section area), and 16 (33%) stained 2+ strongly positive (≥20% section area) for B7-H1. The average number of CD8+ cells per high-power field was 2.1 for positive-staining tumors and 1.0 for negative tumors (p = 0.16). Failure of tumor control with stereotactic radiation (p = 0.029) was significantly greater in the strongly positive B7-H1 tumors. Real-time polymerase chain reaction did not show significant differential expression of microRNA-513 (p = 0.62) or B7-H1 messenger RNA (p = 0.35) between the tumors showing strong and negative immunohistochemical staining for B7-H1 protein. Conclusion Vestibular schwannoma tumors express B7-H1, which has been associated with immune tolerance and adverse disease characteristics in several malignancies. Growing tumors that were surgically removed after failed stereotactic radiation therapy were significantly more likely to strongly express B7-H1 protein, which lends some credibility to the hypothesis that immuno-evasion may play some role in their continued growth. Although clinical trends were seen, greater statistical power is required to evaluate whether B7-H1 expression correlates with more aggressive tumor growth or poorer hearing class. B7-H1 seems to be expressed in equal amounts at the RNA level in all vestibular schwannoma tumors that suggests that differential protein expression is occurring at the posttranscriptional level. However, microRNA-513 does not regulate B7-H1 protein expression in these tumors.

Identifying Predictors of Early Growth Response and Adverse Radiation Effects of Vestibular Schwannomas to Radiosurgery

“…Furthermore, we found that the pre-treatment growth rates for tumors that continue to grow after radiosurgery are comparable to those that responded favorably to radiation and showed a decrease in growth. In other words there was no correlation between post-SRS continued growth and pre-treatment growth rate of VS. Tumors that continue growth after radiosurgery are most likely resistant to radiation because of varying intrinsic molecular properties [17] . It is important to acknowledge that in this study we examined the early changes in growth rates of VS following radiosurgery, and the results seen in early regression following treatment are not a unified concept and not necessarily directly correlated with long-term outcome.…”

Beyond Antoni: A Surgeon's Guide to the Vestibular Schwannoma Microenvironment

“…73 Given the evidence, supporting the upregulation of PD-L1 within VS that have not responded to primary treatment with SRS or surgery, there may be a rationale for immune checkpoint inhibition strategies targeted against the immunosuppressive activity of the PD-L1/PD-1 axis. 30,58 Recombinant anti-PD-1 antibodies have been used to dramatic effect in tumors with high levels of cytotoxic T-cell inhibition, such as melanoma. 74 There is also emerging evidence of the efficacy of such therapies in a subset of glioma patients, and they may represent a promising therapeutic avenue for patients with VS, particularly those with tumors that recur following surgery or SRS with high levels of PD-L1 expression.…”

Comprehensive Immunohistochemical Study of Programmed Cell Death Ligand 1 (PD-L1)

“…(19–22) Several types of cancer have been analyzed for PD-L1 expression, but a comprehensive analyses, including rare germ cell and mesenchymal tumors has not been performed. (10–13, 23–25)…”