Prediction of non-muscle-invasive bladder cancer recurrence by measurement of checkpoint HLAG’s receptor ILT2 on peripheral CD8+ T cells
Metrics: PDF 1121 views | HTML 1762 views | ?
Francois Desgrandchamps1,2,*, Joel LeMaoult1,3,*, Annabelle Goujon1,2, Adrien Riviere1,2, Antonio Rivero-Juarez1,4, Malika Djouadou1,2, Amory de Gouvello1,2, Clement Dumont1,5, Ching-Lien Wu1,3, Stephane Culine1,5, Jerome Verine1,6, Nathalie Rouas-Freiss1,3, Christophe Hennequin1,7, Alexandra Masson-Lecomte1,2 and Edgardo D. Carosella1,3
1CEA, DRF-Francois Jacob Institute, Research Division in Hematology and Immunology (SRHI), Saint-Louis Hospital, Paris, France
2AP-HP, Saint-Louis Hospital, Department of Urology, Paris, France
3University Paris Diderot, Sorbonne Paris Cité, UMR E_5 Institut Universitaire d’Hématologie, Saint-Louis Hospital, Paris, France
4Infectious Diseases Unit, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain
5AP-HP, Saint-Louis Hospital, Department of Medical Oncology, Paris, France
6AP-HP, Saint-Louis Hospital, Department of Pathology, Paris, France
7AP-HP, Saint-Louis Hospital, Department of Radiotherapy, Paris, France
*These authors contributed equally to this work
Joel LeMaoult, email: [email protected]
Keywords: ILT2; HLA-G; immune checkpoint; bladder; cancer
Received: January 20, 2018 Accepted: August 03, 2018 Published: September 04, 2018
Background and Objective: Recurrence of non-muscle invasive bladder cancer (NMIBC) after initial management occurs in 60–70% of patients. Predictive criteria for recurrence remain only clinical and pathological. The aim of this study was to investigate the prognostic significance of the proportion of checkpoint HLA-G’s receptor ILT2-expressing peripheral CD8+ T cells.
Results: The proportion of CD4+ILT2+and CD8+ILT2+ T cells was not increased in NMIBC compared to controls. However, a strong association was found between recurrence and CD8+ILT2+ T cell population levels (p = 0.0006). Two-year recurrence-free survival was 83% in patients with less than 18% CD8+ILT2+ T cells, 39% in the intermediary group, and 12% in patients with more than 46% CD8+ILT2+ T cells. Multivariate analyses demonstrated that the proportion of CD8+ILT2+ T cells was an independent predictive factor for recurrence. Adding CD8+ILT2+ T cells population level to clinical variables increased the predictive accuracy of the model by 4.5%.
Materials and Methods: All patients treated for NMIBC between 2012 and 2014 were included prospectively. Blood samples, tumor and clinico-pathological characteristics were collected. HLA-G expression was measured using IHC, and CD8+ILT2+ T cell levels using flow cytometry. Association between HLA-G and CD8+ILT2+ T cell population levels with NMIBC risk of recurrence was investigated using Cox regression analyses. Prediction was measured using the concordance index statistic.
Conclusions: We demonstrated a strong association between the proportion of circulating CD8+ILT2+ T cells and NMIBC risk of recurrence. Gain in prediction was substantial. If externally validated, such immunological marker could be integrated to predict NMIBC recurrence.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.