Differences between exhausted CD8+ T cells in hepatocellular carcinoma patients with and without uremia.

Abstract

The purpose of this study was to explore the differences between exhausted CD8+ Tcells in hepatocellular carcinoma (HCC) patients with and without uremia. We enrolled 45 uremic patients who were recently diagnosed with HCC into the HCC+ uremia cohort and similar patients with HCC but without uremia into the HCC-only cohort. Lymphocytes were obtained from the two cohorts, and exhausted CD8+ Tcells, comprising PD-1+CD8+, TIM-3+CD8+, and LAG-3+CD8+ Tcells, were sorted and expanded invitro. After expansion, the proportions of PD-1+CD8+, TIM-3+CD8+, and LAG-3+CD8+ Tcells were significantly higher in the HCC-only cohort than in the HCC+ uremia cohort. CD8+ Tcells expressing PD-1, TIM-3, or LAG-3 showed increased tumor reactivity and release of interferon-γ invitro; however, these cells demonstrated weaker anti-tumor activity in HCC+ uremia patients than in HCC-only patients. Among the expanded lymphocytes, only the decreased proportion of PD-1+CD8+ Tcells significantly correlated with the HCC+ uremia cohort (odds ratio of 2.731, p= 0.009). We concluded that peripheral CD8+ Tcells expressing PD-1, TIM-3, or LAG-3 from the HCC+ uremia cohort were dysfunctional invitro. Among these populations, PD-1+CD8+ Tcells were most evident in HCC patients with uremia.