Prediction of non-muscle-invasive bladder cancer recurrence by measurement of checkpoint HLAG’s receptor ILT2 on peripheral CD8+ T cells

Abstract

Background and ObjectiveRecurrence 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.ResultsThe 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 MethodsAll 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.ConclusionsWe 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.

Antagonistic anti-LILRB1 monoclonal antibody regulates antitumor functions of natural killer cells

“…9 10 Previous studies also reported that there is a strong association between the percentage of circulating CD8 + LILRB1 T cells and the recurrence risk of non-muscle-invasive bladder cancer. 41 Taken together, our results and previous reports suggest that LILRB1 expression on NK cells and T cells has prognostic value.…”

“… 9 10 Previous studies also reported that there is a strong association between the percentage of circulating CD8 + LILRB1 T cells and the recurrence risk of non-muscle-invasive bladder cancer. 41 Taken together, our results and previous reports suggest that LILRB1 expression on NK cells and T cells has prognostic value. Although the precise mechanism of the LILRB1 polymorphism in human NK cells is unknown, the expression of LILRB1 on NK cells is linked to particular haplotypes and a polymorphic regulatory region.…”

Prediction tools in non-muscle invasive bladder cancer

“…Its main receptor is ILT2/CD85j and it is expressed on some T lymphocytes: the bond between the ligand and its receptor suppresses the function of natural-killer cells, dendritic cells, cytotoxic T lymphocytes, CD4 + T lymphocytes and the proliferation of T cells. A recent study ( 34 ) analyzed the role of ILT2 on recurrence in non-muscle invasive BCa. This study reported a significant association between the proportion of circulating CD8 + ILT2 + T cells and risk of recurrence.…”

HLA‐G dimer targets Granzyme B pathway to prolong human renal allograft survival

“…Moreover, Gonen-Gross et al (41) discovered that the b2microglobulin-free form of HLA-G also forms disulfide-linked dimers and multimers on the cell surface similar to the dimer form of normal b2microglobulin-associated HLA-G protein, which we demonstrated above in our study. Because b2microglobulin forms a major contact site between LILRB1 and HLA-G that is specific for LILRB1 only, the b2microglobulin-free form may not provide inhibitory signaling through predicting recurrence in bladder cancer (44). However, in our study, we could not determine a significant difference in CD8 + LILRB1 + T cells between RJ and NR groups that excludes these cells as potential marker for kidney graft survival.…”

“…LILRB receptor has potent immunosuppressive effects capable of suppressing alloantigen‐activated T cells and inhibiting TCMR. Recent studies have identified CD8 + LILRBl + T cells in the peripheral blood as a possible biomarker for predicting recurrence in bladder cancer (44). However, in our study, we could not determine a significant difference in CD8 + LILRB1 + T cells between RJ and NR groups that excludes these cells as potential marker for kidney graft survival.…”