A nomogram-based immunoprofile predicts overall survival for previously untreated patients with esophageal squamous cell carcinoma after esophagectomy

Abstract

BackgroundImmunoscore, 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.MethodsThe 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.ResultsSignificant 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.ConclusionsOur nomogram-based immunoprofile can provide more accurate prognosis prediction and is an important complement to the TNM staging system for operable ESCC patients.Electronic supplementary materialThe online version of this article (10.1186/s40425-018-0418-7) contains supplementary material, which is available to authorized users.

Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy

“…In GIST and soft tissue sarcoma, activation of the IDO1 pathway causes immune suppression, decreasing the efficacy of anti-PD-1 therapy [74]. IDO1 has predictive value in some tumors and can be used to stratify and define some cancers [72,75,76]. These findings suggest that IDO1 is a good predictive biomarker and a new approach to cancer treatment ( Fig.…”

Prognostic Values of TIM-3 Expression in Patients With Solid Tumors: A Meta-Analysis and Database Evaluation

“…A total of 3,072 patients, ranging from 30 to 587 patients per study, were involved in our meta-analysis. Among all eligible studies, 13 studies focused on the TIM-3 expression on tumor cells ( 10 – 14 , 28 – 33 , 36 , 39 ), six studies centered on the TIM-3 expression on TILs ( 9 , 34 , 35 , 37 , 38 , 40 ), one study combined the TIM-3 expression on tumor cells and TILs ( 41 ), and one study analyzed the TIM-3 expression on tumor cells and TILs separately ( 42 ). All researches utilized the IHC techniques to detect the expression level of TIM-3.…”

The immune landscape of esophageal cancer

“…CCL4 high CCL20 low ESCC patients have higher 5-year OS rate (73%) than CCL4 low CCL20 low (40.9%) or CCL4 low CCL20 high patients (50%). Recently, nomogram-based immunoprofile, a comprehensive scoring system including TNM stage, PD-L1 expression, and infiltration of CD8 + /Foxp3 + /CD33 + cells, has been developed for prognosis prediction in EC patients [78]. Based on the C-index calculation and receiver operating characteristic (ROC) analysis, this scoring system was able to separate same-stage patients into different risk subgroups, showing superior accuracy for survival prediction compared with TNM staging system.…”