Fudan University Shanghai Cancer Center, Shanghai, China
Ruixuan Geng , Congqi Dai , Angela Wong , Min Qing , Jianjun Hu , Yu Sun , Anthony W.I. Lo , Jin Li
Background : Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role in the immune response against cancer. This study in Chinese patients (pts) with gastric carcinoma (GC) investigated the prognostic significance of PD-L1 expression on tumor cells and its association with tumor-infiltrating lymphocytes (TILs). Methods: 398 archived, formalin-fixed, paraffin-embedded GC samples were collected Oct 2007–Feb 2010 at a single institution from pts with stage I–IV GC after gastric resection and no prior chemo- or radiotherapy. The median age was 60 years (range 21–87 y). TILs were phenotyped and PD-L1 expression on tumor cells was assessed immunohistochemically, using a pre-defined cutoff ( ≥ 5% tumor cells with ≥ 1+). Associations of TIL and PD-L1 expression with clinico-pathologic features were evaluated using a non-zero correlation test. Survival distribution among different subgroups was compared by Kaplan-Meier and a log-rank test. A multivariate Cox regression model was used to investigate prognostic factors (TNM stage, Lauren type, TIL density, PD-L1 expression) for overall survival (OS). The median follow-up time was 44.3 months (range 0.1–79.9 m). Results: PD-L1 expression was observed in 14% of pts. The median OS for PD-L1(-) pts was 61.1 m. The median OS time for the PD-L1(+) pts had not yet been reached. In specimens with PD-L1(+) tumor cells, 96% (55/57) were associated with TILs, and PD-L1 expression on tumor cells was positively associated with TIL densities (P= 0.0018). There was no correlation between PD-L1 expression and Lauren type or TNM stage. Multivariate analysis identified both moderate (HR 0.585; 95% CI, 0.346–0.989; P= 0.045) and high TIL densities (HR 0.109; 95% CI, 0.026–0.462; P= 0.003) as independent factors associated with OS. The association between PD-L1 expression and OS did not reach statistical significance (HR 0.766; 95% CI, 0.452–1.299; P= 0.322). Conclusions: Within the tumor microenvironment, a moderate to high number of TILs is associated with a better clinical outcome and elevated tumor PD-L1 expression. These observations support a possible therapeutic role for PD-L1 inhibitors in a subset of GC pts.
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