Analysis of PDL1 expression and T cells infiltration in 1014 gastric cancer patients.

Abstract

50 Background: Although immune checkpoint inhibitors have demonstrated promising results in melanoma and lung cancer, their effects on gastrointestinal cancer are still under investigation. Understand the prognostic effect of PDL1 expression, infiltration by CD8+ and CD3+ T cells in gastric cancer (GC) might help the identification of candidate patient who might benefit from immunotherapy. Methods: Immunohistochemistry were performed on a tissue microarray including 1,014 GC specimens with PD-L1 antibodies. Immune cell markers CD3 and CD8 were also stained and the quantitative differences were calculated using automated image analysis. Results: 37.8% of the cases showed a membranous PD-L1 expression in tumor cells and 74.9% in tumor infiltrating immune cells. GC patients with high level PDL1 expression in tumor cells or in immune cells were both associated with better survival compared with those with negative expression (5-year OS, 61% vs. 48%, P = 0.000, and 55% vs. 45%, P < 0.0001, respectively). As continuous variables, higher CD3+ and CD8+ cell density were associated with patients’ overall survival and the associations remained as the significant prognostic factors that predict favorable outcomes even after adjusting other unknown confounding factors.(HR: 0.974, 95%CI: 0.963-0.985, P = 0.000; and HR: 0.973, 95%CI: 0.960-0.986, P = 0.000 for CD3 and CD8 respectively). We also observed the close relationship between CD3+, CD8+ cell density and PDL1 expression both in tumor cells and in infiltrating immune cells. Conclusions: This study indicates that PDL1 expression, and TILs in particular, are important prognostic biomarkers. Patients with higher CD8 and CD3 T cell densities also have higher PD-L1 expression, indicating an adaptive immune resistance mechanism may be occurring. The counterintuitive observation that higher PD-L1 expression associating with better patients’ outcome highlights the need to assess both PDL1 expression in all tumor compartments and the characterization of the GC immune microenvironment.