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PD-L1 expression and prognostic impact in glioblastoma
Edjah K Nduom1, Jun Wei1, Nasser K Yaghi1
1Departments of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas (E.K.N., J.W., N.K.Y., N.H., L.-Y.K., K.G., X.L., A.B.H.); Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas (S.Z.); Center for RNA Interference and Non-Coding RNAs, The University of Texas M.D. Anderson Cancer Center, Houston, Texas (C.I.); Flow Cytometry and Cell Imaging Core Facility, The University of Texas M.D. Anderson Cancer Center, Houston, Texas (J.K.B.); Neuropathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas (G.N.F.); Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas (G.A.C.); Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas (C.A.C.); Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas (C.C., K.R.); Lion Biotechnologies, Woodland Hills, California (J.Q.C., L.R.); Dept. of Immunology, H. Lee Moffitt Cancer Center, Tampa, Florida (J.Q.C., L.R.).
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.
