Primary small cell esophageal carcinoma (SCEC) represents a rapidly progressive, aggressive, and rare malignancy without any established treatment strategy. Given the great success of cancer immunotherapy targeting the PD-1/PD-L1 pathway in small cell lung cancer and the central role of CD8+ tumor-infiltrating lymphocytes (TIL) in the response to immune checkpoint inhibitors, we set out to assess the expression pattern and clinical significance of CD8+ TIL in SCESs for the first time.
Totally, 147 SCEC patients underwent surgery at our institution between 1985 and 2019 were collected. The formalin-fixed paraffin-embedded whole tumor sections were immunostained for CD8 with monoclonal mouse antibody. Whole-slide scanning was performed and the tumor regions were annotated by a trained gastrointestinal pathologist. The digital image analysis was then performed to quantify the CD8+ TILs density. Baseline clinicopathological features and outcome data (relapse free survival (RFS) and overall survival (OS)) were correlated with CD8+ TIL states.
The median number of CD8+ TIL cells in SCECs was 111.1 cells/mm2, with the range of 7.5 to 1458.6 cells/mm2. The mean destiny (195.9 cells/mm2) was used as cut-off value stratifying CD8+ TIL positive or negative groups. Positive CD8+ TILs infiltration was found significantly related to macroscopic tumor type (P=0.006), T stage (P=0.007) and TNM stage (P=0.005). Kaplan–Meier analysis showed that patients with positive CD8+ TILs state showed dramatically better RFS (HR = 0.456, 95% CI 0.309–0.674, P=0.0004) and OS (HR = 0.423, 95% CI 0.273–0.657, P=0.0008). Univariate and multivariate Cox regression analyses confirmed that CD8+ TIL state was the significant independent predictor for both RFS and OS, with P values of 0.0140 and 0.0457, respectively.
Here, for the first, we demonstrated that CD8+ TIL destiny was associated with an early stage and favorable clinical outcome in SCECs, supporting its role as a prognostic biomarker. These findings will not only help to improve risk-adapted therapeutic strategies, but also provide a rational basis for further investigation of PD-L1/PD-1-based immunotherapy for patients with SCECs.
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Has not received any funding.
All authors have declared no conflicts of interest.