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

J Immunother Cancer. 2020 Sep;8(2):e000406. doi: 10.1136/jitc-2019-000406.

Abstract

Background: Craniopharyngioma (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.

Methods: We 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.

Results: The 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).

Conclusions: We 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.

Keywords: pathology; tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B7 Antigens / metabolism*
  • B7-H1 Antigen / metabolism*
  • Child
  • Child, Preschool
  • Craniopharyngioma / genetics*
  • Craniopharyngioma / pathology
  • Humans
  • Middle Aged
  • Young Adult

Substances

  • B7 Antigens
  • B7-H1 Antigen
  • CD274 protein, human