2. Academic Validation
  3. ALDH2 Hampers Immune Escape in Liver Hepatocellular Carcinoma through ROS/Nrf2-mediated Autophagy

ALDH2 Hampers Immune Escape in Liver Hepatocellular Carcinoma through ROS/Nrf2-mediated Autophagy

  • Inflammation. 2022 Jun 18. doi: 10.1007/s10753-022-01694-1.
Jingyao Hu 1,  Liang Yang 2,  Xueqiang Peng 2,  Minghuan Mao 3,  Xiaodan Liu 4,  Jianbo Song 5,  Hangyu Li 6
Affiliations

Affiliations

  • 1 The Fourth Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Huanggu District, No. 4, Chongshan East Road, 110000, Liaoning, People's Republic of China. jyhu@cmu.edu.cn.
  • 2 The Third Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, 110000, Liaoning, People's Republic of China.
  • 3 The Fourth Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Huanggu District, No. 4, Chongshan East Road, 110000, Liaoning, People's Republic of China.
  • 4 The Fifth Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, 110000, Liaoning, People's Republic of China.
  • 5 Interventional Department, The Fourth Affiliated Hospital of China Medical University, 110000, Liaoning, People's Republic of China.
  • 6 The Third Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, 110000, Liaoning, People's Republic of China. sj_li_hangyu@sina.com.
PMID: 35715591 DOI: 10.1007/s10753-022-01694-1
Abstract

Aldehyde dehydrogenase 2 (ALDH2) has been implicated in the progression of liver hepatocellular carcinoma (LIHC). The most important feature of LIHC is the immune escape process. This study sets to study the role of ALDH2 in regulating immune escape in LIHC. Bioinformatics analysis was applied to examine the expression of ALDH2 in LIHC and its impact on patients' survival. The effect of ALDH2 expression on malignant phenotype of LIHC cells was assessed by gain-of-function assays. RT-qPCR and Western blot were conducted to examine the expression of related factors, thus investigating the downstream mechanisms of ALDH2. ELISA assay was carried out to measure the level of oxidative stress in cells, and crystal violet staining was conducted to observe the killing effect of T cells on tumor cells. Finally, xenograft assay was carried out to verify the role of ALDH2 in vivo.ALDH2 was poorly expressed in LIHC, which predicted dismal prognoses for patients. ALDH2 inhibited the malignant aggressiveness of LIHC cells. ALDH2 blocked the activation of Nrf2 by suppressing Reactive Oxygen Species (ROS) in LIHC, and Nrf2 significantly reversed the tumor-suppressing properties of ALDH2. Nrf2 hindered Autophagy and led to immune escape of LIHC cells. Moreover, ALDH2 considerably suppressed the growth of xenografts, increased Autophagy and promoted the accumulation of T cells in tumors. In contrast, Nrf2 drastically reversed the repressive effect of ALDH2 on tumor growth.ALDH2 impaired the ROS/Nrf2 axis to promote Autophagy, thereby repressing immune escape in LIHC.

Keywords

ALDH2; Autophagy; Immune escape; Liver hepatocellular carcinoma; Nrf2.

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