PD-L1 expression and prognostic impact in glioblastoma

Authors

Document Type

Article

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.

Medical Subject Headings

Adult; Aged; Animals; B7-H1 Antigen (genetics, metabolism); Biomarkers, Tumor (genetics, metabolism); Brain Neoplasms (genetics, metabolism, pathology); Cell Line, Tumor; Cell Proliferation; Female; Flow Cytometry; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Glioblastoma (genetics, metabolism, pathology); Humans; Immunoenzyme Techniques; Male; Mice; Middle Aged; Neoplasm Staging; Prognosis; RNA, Messenger (genetics); Survival Rate; T-Lymphocytes (metabolism)

Publication Date

2-1-2016

Publication Title

Neuro-oncology

E-ISSN

1523-5866

Volume

18

Issue

2

First Page

195

Last Page

205

PubMed ID

26323609

Digital Object Identifier (DOI)

10.1093/neuonc/nov172

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