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Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy.

ABSTRACT: Ever accumulating evidence indicates that the long-term effects of radiotherapy and chemotherapy largely depend on the induction (or restoration) of an anticancer immune response. Here, we investigated this paradigm in the context of esophageal carcinomas treated by neo-adjuvant radiochemotherapy, in a cohort encompassing 196 patients. We found that the density of the FOXP3+ regulatory T cell (Treg) infiltrate present in the residual tumor (or its scar) correlated with the pathological response (the less Tregs the more pronounced was the histological response) and predicted cancer-specific survival. In contrast, there was no significant clinical impact of the frequency of CD8+ cytotoxic T cells. At difference with breast or colorectal cancer, a loss-of-function allele of toll like receptor 4 (TLR4) improved cancer-specific survival of patients with esophageal cancer. While a loss-of-function allele of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) failed to affect cancer-specific survival, its presence did correlate with an increase in Treg infiltration. Altogether, these results corroborate the notion that the immunosurveillance seals the fate of patients with esophageal carcinomas treated with conventional radiochemotherapy.

SUBMITTER: Vacchelli E

PROVIDER: S-EPMC4673233 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy.

Vacchelli Erika E Semeraro Michaela M Enot David P DP Chaba Kariman K Poirier Colame Vichnou V Dartigues Peggy P Perier Aurelie A Villa Irene I Rusakiewicz Sylvie S Gronnier Caroline C Goéré Diane D Mariette Christophe C Zitvogel Laurence L Kroemer Guido G

Oncotarget 20150801 25

Ever accumulating evidence indicates that the long-term effects of radiotherapy and chemotherapy largely depend on the induction (or restoration) of an anticancer immune response. Here, we investigated this paradigm in the context of esophageal carcinomas treated by neo-adjuvant radiochemotherapy, in a cohort encompassing 196 patients. We found that the density of the FOXP3+ regulatory T cell (Treg) infiltrate present in the residual tumor (or its scar) correlated with the pathological response ...[more]

PMID: 26369701

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Project description:Background and objectivesEsophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal malignancy in most regions of the world. The study aimed to identify risk factors and develop a predictive model for ESCC following surgical resection.Patients and methodsA total of 533 ESCC patients who underwent surgical resection from Suining Central Hospital were enrolled in the study. Cox proportional hazards regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression were performed to identify significant prognostic factors. A prognostic model was constructed, and the receiver operating characteristic (ROC) curve, concordance index (C-index), and decision cure analysis (DCA) were used to evaluate the discrimination and calibration of the prognostic model. Subsequently, we built a nomogram for overall survival (OS) incorporating the prognostic factors, and a calibration plot was employed to assess the consistency between the predicted survival and the observed survival. Based on the model risk score, we split the patients into two subgroups, low-risk and high-risk, and we analyzed the survival time of these two groups using Kaplan-Meier (K-M) survival plots.ResultsFive independent prognosis factors were identified as independent risk factors for OS in ESCC patients who underwent surgical resection. The C-index, ROC curve, and DCA showed that the prognostic model had good predictive accuracy and discriminatory power in the training cohort and validation cohort than other clinical features. A nomogram consisting of prognosis factors showed some superior net benefit. K-M survival plots showed significant differences in OS between the low-risk and high-risk groups. Similar results were observed in the subgroup analysis based on age, grade, and stage. Univariate and multivariate Cox regression analyses revealed that both risk score and risk group are independent prognostic factors in the patient cohort.ConclusionsThis study put forward a novel prognostic model based on clinical features; biopsy data and blood biomarkers may represent a promising tool for estimating OS in ESCC patients.

Dataset Information

Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy.

Publications

Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy.

Similar Datasets

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