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<p>Glioblastoma (GBM) is a highly lethal brain tumor resistant to immunotherapy such as immune checkpoint inhibitors, partly because of an immunosuppressive tumor microenvironment and blood–brain barrier (BBB) dysfunction. Although bevacizumab can remodel the tumor vasculature, the relationship between BBB-related vascular changes and immune cell infiltration in GBM remains poorly understood. We analyzed human isocitrate dehydrogenase (<i>IDH</i>)-wildtype GBM tissues obtained after bevacizumab administration. Immunohistochemistry was performed for CD34 and plasmalemma vesicle-associated protein (PLVAP/PV-1), an endothelial marker associated with BBB disruption. Infiltrating T cells (CD3, CD8) and tumor-associated macrophages/microglia (TAMs; CD163) were also examined. PLVAP was broadly expressed in tumor vessels of untreated GBM and significantly reduced after bevacizumab administration, with marked downregulation in 3 of 10 treated cases. Among the 10 treated cases, significant increases in T-cell and cytotoxic T-lymphocyte infiltration were seen in PLVAP-low GBM compared with PLVAP-high GBM. TAM density did not differ significantly between groups but tended to be higher in the PLVAP-low group. These findings suggest that the bevacizumab-associated reduction of PLVAP expression is linked to increased T-cell infiltration in a subset of GBM cases. PLVAP may serve as an auxiliary histological marker for evaluating bevacizumab-related vascular/BBB remodeling in clinical specimens.</p>

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Association between PLVAP downregulation and increased lymphocyte infiltration in newly diagnosed glioblastoma treated with bevacizumab

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Hiroaki Matsuzaki,
  • Shukang Zhao,
  • Yoshihiro Komohara,
  • Cheng Pan,
  • Rin Yamada,
  • Daiki Yoshii,
  • Yukio Fujiwara,
  • Hiromu Yano,
  • Ai Iwauchi,
  • Nei Fukasawa,
  • Masayuki Shimoda,
  • Akitake Mukasa,
  • Toshihide Tanaka

摘要

Glioblastoma (GBM) is a highly lethal brain tumor resistant to immunotherapy such as immune checkpoint inhibitors, partly because of an immunosuppressive tumor microenvironment and blood–brain barrier (BBB) dysfunction. Although bevacizumab can remodel the tumor vasculature, the relationship between BBB-related vascular changes and immune cell infiltration in GBM remains poorly understood. We analyzed human isocitrate dehydrogenase (IDH)-wildtype GBM tissues obtained after bevacizumab administration. Immunohistochemistry was performed for CD34 and plasmalemma vesicle-associated protein (PLVAP/PV-1), an endothelial marker associated with BBB disruption. Infiltrating T cells (CD3, CD8) and tumor-associated macrophages/microglia (TAMs; CD163) were also examined. PLVAP was broadly expressed in tumor vessels of untreated GBM and significantly reduced after bevacizumab administration, with marked downregulation in 3 of 10 treated cases. Among the 10 treated cases, significant increases in T-cell and cytotoxic T-lymphocyte infiltration were seen in PLVAP-low GBM compared with PLVAP-high GBM. TAM density did not differ significantly between groups but tended to be higher in the PLVAP-low group. These findings suggest that the bevacizumab-associated reduction of PLVAP expression is linked to increased T-cell infiltration in a subset of GBM cases. PLVAP may serve as an auxiliary histological marker for evaluating bevacizumab-related vascular/BBB remodeling in clinical specimens.