Combined prognostic effect of PD-L1 expression and immunoscore in microsatellite-unstable advanced gastric cancers

BACKGROUND The aim of this study was to evaluate how programmed death-ligand-1 (PD-L1) expression is linked to the immunoscore in the context of the tumor microenvironment and to assess the differential prognostic value of PD-L1 expression according to the immunoscore in 153 patients with microsatellite instability-high (MSI-H) advanced gastric cancer (GC). RESULTS We found that T-PD-L1 (+) and I-PD-L1 (+) were significantly associated with a high immunoscore. The integrated PD-L1 expression of tumor and immune cells was not significantly correlated with the overall survival (OS) of patients. However, a combined survival analysis of PD-L1 expression and immunoscore revealed four distinct subgroups with a statistically significant difference in OS. That is, the PD-L1 (+)/immunoscoreLow group showed the worst and the PD-L1 (+)/immunoscoreHigh group showed the best prognosis. Furthermore, a multivariate analysis revealed that the combined status of PD-L1 expression and immunoscore was an independent and significant prognostic factor for OS in patients with MSI-H GC. MATERIALS AND METHODS The immunoscore was quantified by the number of high-density areas of CD3+ and CD8+ tumor infiltrating lymphocytes both in the tumor regions and compartments (i.e., epithelial and stromal compartments of the tumor center and the invasive front), the scores of which range from I0 to I8. By using immunohistochemistry, the expression of PD-L1 was also analyzed in tumor cells (T-PD-L1) and immune cells (I-PD-L1) using four different cut-off values (1%, 5%, 10% and 50%). CONCLUSIONS Our study revealed that PD-L1 expression is associated with the corresponding immunoscore and that the immunoscore can be a relevant marker for the determination of the prognostic role of PD-L1 expression in MSI-H GCs.