PD-L1 expression and prognostic impact in glioblastoma

Edjah K. Nduom, Jun Wei, Nasser K. Yaghi, Neal Huang, Ling Yuan Kong, Konrad Gabrusiewicz, Xiaoyang Ling, Shouhao Zhou, Cristina Ivan, Jie Qing Chen, Jared K. Burks, Greg N. Fuller, George A. Calin, Charles A. Conrad, Caitlin Creasy, Krit Ritthipichai, Laszlo Radvanyi, Amy B. Heimberger

Research output: Contribution to journalArticlepeer-review

243 Scopus citations

Abstract

Background Therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule-4 (CTLA-4) and PD-1/PD-L1 has demonstrated tumor regression in clinical trials, and phase 2 trials are ongoing in glioblastoma (GBM). Previous reports have suggested that responses are more frequent in patients with tumors that express PD-L1; however, this has been disputed. At issue is the validation of PD-L1 biomarker assays and prognostic impact. Methods Using immunohistochemical analysis, we measured the incidence of PD-L1 expression in 94 patients with GBM. We categorized our results according to the total number of PD-L1-expressing cells within the GBMs and then validated this finding in ex vivo GBM flow cytometry with further analysis of the T cell populations. We then evaluated the association between PD-L1 expression and median survival time using the protein expression datasets and mRNA from The Cancer Genome Atlas. Results The median percentage of PD-L1-expressing cells in GBM by cell surface staining is 2.77% (range: 0%-86.6%; n = 92), which is similar to the percentage found by ex vivo flow cytometry. The majority of GBM patients (61%) had tumors with at least 1% or more PD-L1-positive cells, and 38% had at least 5% or greater PD-L1 expression. PD-L1 is commonly expressed on the GBM-infiltrating T cells. Expression of both PD-L1 and PD-1 are negative prognosticators for GBM outcome. Conclusions The incidence of PD-L1 expression in GBM patients is frequent but is confined to a minority subpopulation, similar to other malignancies that have been profiled for PD-L1 expression. Higher expression of PD-L1 is correlated with worse outcome.

Original languageEnglish (US)
Pages (from-to)195-205
Number of pages11
JournalNeuro-oncology
Volume18
Issue number2
DOIs
StatePublished - Feb 1 2016

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

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