The integration of proportion and cell counts of stromal, not intratumoral, PD-1+ tumor-infiltrating lymphocytes has prognostic significance in esophageal squamous cell carcinoma.

The present study aimed to investigate the prognostic effect of intratumoral and stromal exhausted tumor-infiltrating lymphocytes (TILs) on operable esophageal cancer patients. We performed a retrospective cohort study by consecutively recruiting 142 patients with esophageal cancer. The proportion and cell counts of intratumoral and stromal PD-1+ TILs in tumor microenvironment were independently evaluated by two pathologists. Neither proportion nor cell counts of intratumoral PD-1+ TILs was associated with prognosis (p > 0.05). However, patients with the proportion of stromal PD1+ TILs >20% had the median overall survival (OS) at 19 months, significantly longer than those with the proportion = 20%. The adjusted hazard ratio (HR) was 1.49 (95%CI 0.82, 2.69). Patients with cell counts of stromal PD1+ TILs = 18/ high-power field (HPF) had the median disease-free survival (DFS) at 10 months. However, patients with cell counts>18/HPF had the median DFS at 48 months (p = 0.037), and the adjusted HR was 0.59 (95%CI 0.35, 1.01). Compared with patients with proportion = 20% and cell counts >18/HPF of stromal PD1+ TILs, patients with proportion = 20% and cell counts = 18/HPF, proportion >20% and cell counts >18/HPF, and proportion >20% and cell counts = 18/HPF, had the adjusted HRs increased to 3.73, 3.36 and 3.99 for DFS (p for trend being 0.030) and the adjusted HRs increased to 2.95, 3.64 and 3.82 (p for trend being 0.015) for OS, respectively. The integration of proportion and cell counts of PD-1+ stromal TILs has a significant association with the relapse and overall survival of esophageal cancer patients. Further prospective studies are warranted.