Prediction of non-muscle-invasive bladder cancer recurrence by measurement of checkpoint HLAG’s receptor ILT2 on peripheral CD8+ T cells
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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: Joel.LeMaoult@cea.fr
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.
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