Naturally occurring, tumor-specific CD8+ T cells in patients with hepatocellular carcinoma display a clear immunodominance

2012 ◽  
Vol 50 (01) ◽  
Author(s):  
T Flecken ◽  
N Schmidt ◽  
S Hild ◽  
O Drognitz ◽  
DA Price ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Cd8 T Cells ◽  
Naturally Occurring

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

2020 ◽  
Author(s):  
Xiaohong Chen ◽  
Jianzhou Zou ◽  
Bo Shen ◽  
Wenlv Lv ◽  
Xuesen Cao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Cd8 T Cells ◽  
Ifn Γ ◽  
Uremic Patients ◽  
Anti Tumor Activity

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.

scholarly journals HBsAg-specific CD8+ T cells as an indispensable trigger to induce murine hepatocellular carcinoma

2019 ◽  
Vol 18 (1) ◽  
pp. 128-137 ◽  
Author(s):  
Xiaolei Hao ◽  
Yongyan Chen ◽  
Lu Bai ◽  
Haiming Wei ◽  
Rui Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Cd8 T Cells

scholarly journals Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients

2008 ◽  
Vol 58 (3) ◽  
pp. 325-338 ◽  
Author(s):  
Ashley J. Knights ◽  
Natko Nuber ◽  
Christopher W. Thomson ◽  
Olga de la Rosa ◽  
Elke Jäger ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Tumour Antigen ◽  
Naturally Occurring

scholarly journals Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using Multiplex Quantitative Analysis

2020 ◽  
Author(s):  
Mengzhou Guo ◽  
Feifei Yuan ◽  
Feng Qi ◽  
Jialei Sun ◽  
Qianwen Rao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Prognostic Significance ◽  
Normal Liver ◽  
Patient Stratification ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Low Levels

Abstract Background: fibrinogen-like protein 1 (FGL1) - Lymphocyte activating gene 3 (LAG-3) pathway is a promising immunotherapeutic target and has synergistic effect with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1). However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unknown.Methods: The levels of LAG-3, FGL1, PD-L1 and cytotoxic T (CD8+T) cells in 143 HCC patients were assessed by multiplex immunofluorescence. Associations between the marker’s expression and clinical significances were studied.Results: We found FGL1 and LAG-3 densities were elevated while PD-L1 and CD8 were decreased in HCC tissues compared to adjacent normal liver tissues. High levels of FGL1 were strongly associated with high densities of LAG-3+cells but not PD-L1. CD8+ T cells densities had positive correlation with PD-L1 levels and negative association with FGL1 expression. Elevated densities of LAG-3+cells and low levels of CD8+ T cells were correlated with poor disease outcome. Moreover, LAG-3+cells deteriorated patient stratification based on the abundance of CD8+ T cells. Patients with positive PD-L1 expression on tumor cells (PD-L1 TC+) tended to have an improved survival than that with negative PD-L1 expression on tumor cells (PD-L1 TC-). Furthermore, PD-L1 TC- in combination with high densities of LAG-3+cells showed the worst prognosis, and PD-L1 TC+ patients with low densities of LAG-3+cells had the best prognosis.Conclusions: LAG-3, FGL1, PD-L1 and CD8 have distinct tissue distribution and relationships with each other. High levels of LAG-3+cells and CD8+ T cells represent unfavorable and favorable prognostic biomarkers for HCC respectively.

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