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

• Published in: Journal for immunotherapy of cancer 2018-10, Vol.6 (1), p.100-100, Article 100
• Main Authors: Duan, Jingjing, Xie, Yongwei, Qu, Lijuan, Wang, Lingxiong, Zhou, Shunkai, Wang, Yu, Fan, Zhongyi, Yang, Shengsheng, Jiao, Shunchang
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies; Antigens; Cancer; Cancer patients; Cancer therapies; Care and treatment; CD8; Esophageal cancer; Esophageal squamous cell carcinoma; Esophageal Squamous Cell Carcinoma - immunology; Esophageal Squamous Cell Carcinoma - mortality; Esophageal Squamous Cell Carcinoma - pathology; Esophagectomy - methods; Female; Health aspects; Humans; Immunoprofile; Immunotherapy; Lymphocytes; Male; Medical prognosis; Medical research; Middle Aged; Mortality; Nomogram; Nomograms; Patient outcomes; PD-L1; Prognosis; Squamous cell carcinoma; Survival Analysis; Tumors
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/s40425-018-0418-7

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. 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. 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. Our nomogram-based immunoprofile can provide more accurate prognosis prediction and is an important complement to the TNM staging system for operable ESCC patients.