Background: Immunoscore, as a prognostic tool defined to quantify in situ immune cell infiltrates, appears to be superior to the TNM staging system. In esophageal squamous cell carcinoma (ESCC), no immunoscore has been established; however, in situ tumor immunology is recognized as highly important. Our study aimed to construct a comprehensive immunoprofile for ESCC. Methods: The infiltration of four immune cell types (CD8+/CD4+/Foxp3+/CD33+ cells), the expression of both inhibitory (PD-1/PD-L1/Tim-3/LAG-3) and stimulatory checkpoints (OX-40/ICOS), and IDO1 were evaluated by IHC staining and multi-color immunofluorescence in two independent cohorts (95 patients in the primary cohort and 55 patients in the validation cohort). The association with patients' overall survival was analyzed by the Kaplan-Meier method and the Cox model. Nomogram-based immunoprofile was established using the independent prognostic variables. To determine its predictive accuracy and discriminatory capacity, the C-index and calibration curve were calculated. Results: Significant correlation of PD-L1 expression in tumor cells with PD-1+ T cell infiltration was found (P = 0.035), indicating the activation of the inhibitory PD-1/PD-L1 pathway in ESCC cases. More PD-L1+ ICs, Tim-3+ ICs and LAG-3+ ICs were found in the CD8-rich tumor microenvironment, which is in accordance with the feedback nature of immune system. After adjustment by TNM stage, four immune variables including the infiltration of CD8+/Foxp3+/CD33+ cells and the PD-L1 expression by tumor cells were selected to construct a prognostic nomogram. The calibration curves showed good accuracy of the nomogram for survival prediction. To overcome the complexity of applying a nomogram in a clinical setting, a simple immunoprofile was then established according to the points of each factor from the nomogram. Our immunoprofile model could separate same-stage patients into different risk subgroups, and showed superior accuracy for survival prediction than the TNM staging system based on the C-index calculation and ROC analysis. Conclusions: Our nomogram-based immunoprofile can provide more accurate prognosis prediction and is an important complement to the TNM staging system for operable ESCC patients.
Duan, J., Xie, Y., Qu, L., Wang, L., Zhou, S., Wang, Y., … Jiao, S. (2018). A nomogram-based immunoprofile predicts overall survival for previously untreated patients with esophageal squamous cell carcinoma after esophagectomy 11 Medical and Health Sciences 1107 Immunology. Journal for ImmunoTherapy of Cancer, 6(1). https://doi.org/10.1186/s40425-018-0418-7