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

World Neurosurg. 2020 Mar:135:e12-e18. doi: 10.1016/j.wneu.2019.10.044. Epub 2019 Oct 16.

Abstract

Background: The high expression across multiple tumor types and restricted expression in normal tissues make B7-H3 an attractive target for immunotherapy. So far, little is known about the clinical significance of B7-H3 expression in meningiomas. We conducted this study to address this issue in a cohort of 242 patients from a single institution.

Methods: Expression profiles of immune checkpoint proteins (programmed death-ligand 1, B7-H3, lymphocyte activation gene-3, programmed death 1, and V-domain Ig suppressor of T cell activation) were explored by immunohistochemistry in a meningioma test cohort (n = 8). Role of B7-H3 expression was further assessed in an expanded patient cohort (n = 234) using immunohistochemical tissue microarray analysis.

Results: B7-H3 expression was significantly greater than all immune checkpoint proteins studied in the tested cohort. B7-H3 was detected with different degrees in all meningioma specimens, predominantly on tumor cell membranes and in cytoplasm. Tumors were classified as B7-H3 high or low group depending on immunohistochemistry histoscore (median histoscore 111.06; range, 7.313-212.008). B7-H3 expression was statistically correlated with patient sex (P = 0.0297), tumor histopathologic subtypes (P = 0.0262), and radiotherapy after surgery (P = 0.0028). However, no significant differences were observed in patient age, tumor location, and grade and extent of resection between groups. Similarly, there was no significant difference in progression-free survival and overall survival between B7-H3 high and low group.

Conclusions: Our study indicates variable expression and clinical role of B7-H3 in meningiomas, suggesting its potential as an immunotherapeutic target in the future.

Keywords: B7-H3; Checkpoint; Immunotherapy; Meningioma; PD-L1; VISTA.

MeSH terms

  • Adult
  • Aged
  • B7 Antigens / metabolism*
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / analysis*
  • Female
  • Humans
  • Immunotherapy / methods
  • Male
  • Meningeal Neoplasms / metabolism
  • Meningeal Neoplasms / pathology*
  • Meningioma / metabolism*
  • Meningioma / pathology
  • Middle Aged
  • Tissue Array Analysis / methods

Substances

  • B7 Antigens
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CD276 protein, human