Immunoscore based on CD3+ and cytotoxic CD8+ T-lymphocyte densities predicts prognosis and chemotherapy efficacy in esophageal squamous cell carcinoma.

The current American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis (AJCC/UICC-TNM) staging system for esophageal squamous cell carcinoma (ESCC) does not incorporate an immune-based classification. This study aimed to evaluate the prognostic value of the Immunoscore (IS), based on the densities of CD3+ and cytotoxic CD8+ T lymphocytes, and its ability to predict the efficacy of chemotherapy in patients with ESCC. The IS was determined by immunohistochemical staining for CD3 and CD8 and was calculated according to the densities of CD3+ and CD8+ cells in the tumor center (CT) and invasive margin (IM). A total of 255 patients with previously untreated ESCC who underwent curative resection were randomly assigned to training and validation sets. Among them, 169 received postoperative chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were the endpoints of the prognostic analyses. In the training set, patients with a high IS had the lowest risk of recurrence. The 5-year RFS rates were 9.7%, 44.7%, and 90.1% among patients with low, intermediate, and high IS values, respectively (hazard ratio [HR] for high vs. low IS, 0.29; P<0.001). A high IS was also significantly associated with prolonged OS (P<0.001). Multivariable Cox regression analysis showed that the associations of IS with RFS and OS were independent of clinicopathological variables (HR for high vs. low IS: 0.29 for RFS and 0.53 for OS; both P<0.001). The IS accounted for the largest proportion of the total χ2 statistic in predicting both RFS and OS (P<0.001). The IS was also significantly associated with RFS and OS among patients who received postoperative chemotherapy (both P<0.001). These findings were further confirmed in the validation set. The IS provides more accurate prognostic stratification and prediction of chemotherapy efficacy. It may complement the AJCC/UICC-TNM staging system in patients with operable ESCC.