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- Title
Differences between exhausted CD8<sup>+</sup> T cells in hepatocellular carcinoma patients with and without uremia.
- Authors
Xiaohong, Chen; Jianzhou, Zou; Bo, Shen; Wenlv, Lv; Xuesen, Cao; Fangfang, Xiang
- Abstract
The purpose of this study was to explore the differences between exhausted CD8+ T cells 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+ T cells, comprising PD-1+CD8+, TIM-3+CD8+, and LAG-3+CD8+ T cells, were sorted and expanded in vitro. After expansion, the proportions of PD-1+CD8+, TIM-3+CD8+, and LAG-3+CD8+ T cells were significantly higher in the HCC-only cohort than in the HCC + uremia cohort. CD8+ T cells expressing PD-1, TIM-3, or LAG-3 showed increased tumor reactivity and release of interferon-γ in vitro; 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+ T cells significantly correlated with the HCC + uremia cohort (odds ratio of 2.731, p = 0.009). We concluded that 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 most evident in HCC patients with uremia.
- Subjects
UREMIA; HEPATOCELLULAR carcinoma; ODDS ratio; LYMPHOCYTES; PROGRAMMED cell death 1 receptors
- Publication
Canadian Journal of Physiology & Pharmacology, 2021, Vol 99, Issue 4, p395
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2019-0641