Prediction of Non-muscle-invasive Bladder Cancer Recurrence by Measurement of Checkpoint HLAG's Receptor ILT2 on Peripheral CD8 T Cells

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 CD4ILT2and CD8ILT2 T cells was not increased in NMIBC compared to controls. However, a strong association was found between recurrence and CD8ILT2 T cell population levels ( = 0.0006). Two-year recurrence-free survival was 83% in patients with less than 18% CD8ILT2 T cells, 39% in the intermediary group, and 12% in patients with more than 46% CD8ILT2 T cells. Multivariate analyses demonstrated that the proportion of CD8ILT2 T cells was an independent predictive factor for recurrence. Adding CD8ILT2 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 CD8ILT2 T cell levels using flow cytometry. Association between HLA-G and CD8ILT2 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 CD8ILT2 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.