Association between PD-L1 Expression on Tumour-Infiltrating Lymphocytes and Overall Survival in Patients with Gastric Cancer

Abstract

Purpose Targeting of the PD-1/PD-L1 signalling pathway is a promising treatment strategy in several cancers. The aim of this study was to assess the expression of PD-L1 on tumour cells and tumour-infiltrating lymphocytes (TILs) in gastric cancer (GC) and its prognostic impact.Materials and Methods A total of 240 patients who were diagnosed with GC at Sun Yat-sen University Cancer Centre (SYSUCC) from May 2008 to December 2013 were included in this study. PD-L1 expression was detected by immunohistochemistry (IHC) in all GC tumour specimens. The Cox proportional hazard regression model was used to assess the association between PD-L1 expression and overall survival (OS).Results The positive rates of PD-L1 expression on tumour cells and TILs were 74.8% and 65.8%, respectively. Patients with poor tumour differentiation had higher positive rates of PD-L1 expression on tumour cells (p=0.023). There was no significant association between PD-L1 expression on tumour cells and other clinicopathological data. In TILs, PD-L1 expression was significantly higher in patients who underwent surgery (p=0.031) and were in the late stage (p=0.021) than those without surgery and in the early stage. Patients with positive PD-L1 expression on TILs had a significantly shorter five-year OS than those with negative PD-L1 expression (14.2 vs 18.3; p=0.001); therefore, PD-L1 expression on TILs is an independent prognostic factor. However, PD-L1 expression on tumour cells is not associated with OS (p=0.945).Conclusion Our findings suggest that PD-L1 expression on TILs may be a predictive factor for immunotherapy of PD-1/PD-L1 pathway inhibitors.

Programmed death‐ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER2‐negative status

“…However, the relationship between PD-L1 expression and the prognosis remains controversial in GC. Many researches showed that PD-L1 expression had a negative impact on patient survival [24][25][26][27], but some studies indicated that PD-L1 positivity was associated with favorable outcomes [16,28]. In our study, PD-L1 expression in GC was related to some adverse clinicopathological characteristics, which was observed more frequently in advanced GCs occurred in the older patients and with bigger tumor size.…”

Clinicopathological and prognostic features of Epstein‐Barr virus infection, microsatellite instability, and PD‐L1 expression in gastric cancer

“…As only 25 patients were PD‐L1‐positive, these may have limited the survival analysis. Furthermore, this variability in reported outcomes might be influenced in part by the patient cohort, since we had 55.1% of GCs staged as I/II and high PD‐L1 levels seems to be related to more advanced stages …”

“…In general, studies have small populations and few meta-analyses have shown a correlation between PD-L1 and prognosis. 25,26,35,36 Some authors showed that PD-L1-positive expression was associated to poor prognosis in advanced GC, 37,38 whereas other studies proposed that increased PD-L1 expression are related to a better prognosis. 34,39 Still, some authors have shown no impact on survival.…”

“…Furthermore, this variability in reported outcomes might be influenced in part by the patient cohort, since we had 55.1% of GCs staged as I/II and high PD-L1 levels seems to be related to more advanced stages. 26,37,39 Recently, with the approval of PD-1 monoclonal antibody pembrolizumab and nivolumab by US Food and Drug Administration (FDA) and the currently undergoing trials of anti-PD-1/PD-L1…”

Vírus Epstein-Barr, Instabilidade De Microssatélite E Expressão De Pd-L1 Nos Adenocarcinomas Gástricos: Aspectos Clínico-Patológicos E Prognósticos.

“…Em geral, os estudos envolvem casuísticas pequenas e poucas metaanálises apresentam associação entre PD-L1 e prognóstico 80,81,123,127. Alguns autores mostraram que a positividade para PD-L1 está associada a pior prognóstico no CG avançado,128,129 enquanto outros propõe que o aumento da expressão de PD-L1 relaciona-se a melhor prognóstico 83,87. Ainda assim, alguns autores não mostraram nenhum impacto na sobrevida 42,109.…”