Effects and mechanisms of liver cancer cell-derived LC3B + extracellular vesicles on the exhaustion of CD8 + T cells
10.3760/cma.j.cn112309-20210603-00191
- VernacularTitle:肝癌细胞来源LC3B阳性的细胞外囊泡诱导CD8 +T细胞耗竭的作用机制研究
- Author:
Yongqiang CHEN
1
;
Lu ZHENG
;
Zhongsong MAN
;
Yue ZHANG
;
Peng WANG
;
Lu WANG
;
Juan ZHOU
;
Guoping NIU
Author Information
1. 徐州市中心医院检验科，徐州市医学科学研究所，徐州 221009
- Keywords:
Liver cancer;
Extracellular vesicles;
CD8 + T cell exhaustion;
HSP90α
- From:
Chinese Journal of Microbiology and Immunology
2022;42(3):202-208
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the potential molecular mechanisms of liver cancer cell-derived secretory autophagosomes, extracellular vesicles expressing LC3B (LC3B + EVs), in promoting the exhaustion of CD8 + T cells. Methods:The proportions of LC3B + EVs and PD-1 + CD8 + T cells in peripheral blood and ascites of liver cancer patients were measured by flow cytometry. Spearman correlation test was used to analyze the correlation between the proportions of LC3B + EVs and PD-1 + CD8 + T cells. Peripheral blood mononuclear cells (PBMCs) from healthy donors were treated with LC3B + EVs or heat shock protein 90α (HSP90α) blocking antibody-pretreated LC3B + EVs for 72 h in the presence of αCD3/CD28 antibodies and IL-2 in vitro. The proportions of PD-1 + CD8 + T and IFN-γ + CD8 + T cells and the concentrations of IL-2, TNF-α and IFN-γ in the supernatants were all detected by flow cytometry. Results:The proportions of LC3B + EVs and HSP90α + LC3B + EVs in plasma and ascites from liver cancer patients were significantly higher than those in healthy control group and non-cancerous ascites group. The level of plasma LC3B + EVs, especially HSP90α + LC3B + EVs, was significantly correlated with the percentage of exhausted PD-1 + CD8 + T cells. In addition, LC3B + EVs from human liver cancer cells up-regulated the percentage of exhausted CD8 + T cells in vitro. However, LC3B + EVs pretreated with HSP90α blocking antibody could significantly inhibit LC3B + EVs-induced CD8 + T cell exhaustion. Conclusions:Liver cancer cell-derived LC3B + EVs could effectively induce CD8 + T cell exhaustion mainly through the membrane-bound HSP90α.
