J Pathol Transl Med.  2017 Jan;51(1):40-48. 10.4132/jptm.2016.08.31.

PD-L1 Expression and Combined Status of PD-L1/PD-1–Positive Tumor Infiltrating Mononuclear Cell Density Predict Prognosis in Glioblastoma Patients

• Han J
• Hong Y
• Lee YS

• KMID: 2367679
• DOI: http://doi.org/10.4132/jptm.2016.08.31

Abstract

BACKGROUND
Programmed death ligand 1 (PD-L1) in tumor cells is known to promote immune escape of cancer by interacting with programmed cell death 1 (PD-1) in tumor infiltrating immune cells. Immunotherapy targeting these molecules is emerging as a new strategy for the treatment of glioblastoma (GBM). Understanding the relationship between the PD-L1/PD-1 axis and prognosis in GBM patients may be helpful to predict the effects of immunotherapy.
METHODS
PD-L1 expression and PD-1-positive tumor infiltrating mononuclear cell (PD-1+tumor infiltrating mononuclear cell [TIMC]) density were evaluated using tissue microarray containing 54 GBM cases by immunohistochemical analysis; the associations with patient clinical outcomes were evaluated.
RESULTS
PD-L1 expression and high PD-1+TIMC density were observed in 31.5% and 50% of GBM cases, respectively. High expression of PD-L1 in tumor cells was an independent and significant predictive factor for worse overall survival (OS; hazard ratio, 4.958; p = .007) but was not a significant factor in disease-free survival (DFS). PD-1+TIMC density was not correlated with OS or DFS. When patients were classified based on PD-1 expression and PD-1+TIMC density, patients with PD-L1+/PD-1+TIMC low status had the shortest OS (13 months, p = .009) and DFS (7 months, p = .053).
CONCLUSIONS
PD-L1 expression in GBM was an independent prognostic factor for poor OS. In addition, combined status of PD-L1 expression and PD-1+TIMC density also predicted patient outcomes, suggesting that the therapeutic role of the PD-1/PD-L1 axis should be considered in the context of GBM immunity.

Keyword

Glioblastoma; Programmed cell death 1; Programmed death ligand 1

MeSH Terms

Cell Count*
Cell Death
Disease-Free Survival
Glioblastoma*
Humans
Immunotherapy
Prognosis*
United Nations

Figure

• 

  Fig. 1. Immunohistochemical staining pattern for programmed death ligand 1 (PD-L1) and programmed cell death 1 (PD-1). (A) Human placenta tissue as a positive control for endogenous PD-L1. PD-L1 positive tumor cells showing membranous and cytoplasmic staining with moderate (B) and weak (C) intensity. (D) PD-L1 negative tumor cells. (E) Tonsil tissue as a positive control for endogenous PD-1. Glioblastoma with high density (F) and low density (G) of PD-1 positive tumor infiltrating mononuclear cells (PD-1+tumor infiltrating mononuclear cell [TIMC]). (H) PD-1+TIMC consists of lymphocytes (most) and macrophages (some).

• 

  Fig. 2. Kaplan-Meier plots for overall survival and disease-free survival of glioblastoma patients according to the programmed death ligand 1 (PD-L1) expression status (A, B) and disease-free survival (C, D). TIMC, tumor infiltrating mononuclear cell.

• 

  Fig. 3. Kaplan-Meier curves for overall survival (A, C, E, G), and disease free survival (B, D, F, H) of patients with positive or negative expression of programmed death ligand 1 (PD-L1) and high or low density of programmed cell death 1 (PD-1)+tumor infiltrating mononuclear cell (TIMC).

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