Differences between Exhausted CD8+ T cells in Hepatocellular Carcinoma Patients with and without Uremia

Purpose: To explore the differences between exhausted CD8+ T cells in HCC patients with and without uremia. Methods: We enrolled 45 uremic patients who were recently diagnosed with HCC into the HCC uremia cohort. We also enrolled similar patients with HCC but without uremia; this was the HCC only cohort. Lymphocytes were obtained from the two cohorts and exhausted CD8+ T cells, comprising PD-1+CD8+, TIM-3+CD8+, and LAG-3+CD8+ T cells, were sorted and expanded in vitro. Results: The proportions of PD-1+CD8+, TIM-3+CD8+, and LAG-3+CD8+ T cells after expansion were significantly higher in the HCC only cohort as compared to those in the HCC uremia cohort. CD8+ T cells expressing PD-1, TIM-3, or LAG-3 showed increased tumor reactivity and release of IFN-γ in vitro; however, these cells demonstrated weaker anti-tumor activity in HCC uremia patients than those in HCC patients without uremia. Among the expanded lymphocytes, only the decreased proportion of PD-1+CD8+ T cells correlated with the HCC uremia cohort (OR: 2.731, p=0.009). Conclusions: Peripheral CD8+ T cells expressing PD-1, TIM-3, or LAG-3 from the HCC uremia cohort were dysfunctional in vitro. Among these populations, PD-1+CD8+ T cells were the most predominant in HCC patients with uremia.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author