PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells

Sep 24, 2026

Uploaded by Margaret

PRDX2 is highly expressed across cancers and linked to tumor proliferation, yet its precise role in tumor immune regulation is not fully defined. This study examines how PRDX2, strongly expressed in lung adenocarcinoma, influences T cells within the tumor immune microenvironment and identifies its immune action target to promote immune escape. Using mouse models and cellular co-culture, the work tests PRDX2 effects on tumor growth, apoptosis, T-cell infiltration, and function.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

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Abstract

Background

Methods

Results

Conclusions

Introduction

Dong et al. Journal of Translational Medicine (2025) 23:81 [https://doi.org/10.1186/s12967-024-05888-z](https://doi.org/10.1186/s12967-024-05888-z) Journal of Translational Medicine RESEARCH Open Access PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells Yunjia Dong 1,2, Anqi Cheng 1,3†, Jiawei Zhou 1,2, Jianqiang Guo 1,2, Yafeng Liu 1,3, Xuan Li 1,2, Maoqian Chen 1,2, Dong Hu5,6* and Jing Wu4* Abstract Background PRDX2 is significantly expressed in various cancers and is associated with the proliferation of tumor cells. Nonetheless, the precise mechanism of PRDX2 in tumor immunity remains incompletely understood. This study aims to investigate the impact of PRDX2, which is highly expressed in lung adenocarcinoma, onT cells in the tumor immune microenvironment, and its immune action target to promote the immune escape of lung cancer cells, to provide a theoretical basis for lung adenocarcinoma treatment with PRDX2 as the target. Methods Mouse animal models to verify the effect of Conoidin A treatment on tumor growth and T cell infiltration. Flow cytometry and Western blot verified tumor cell apoptosis in the in vitro co-culture system as well as granzyme B and perforin expression inT cells. RNA-Seq was used to obtain the downstream immune molecule. si-RNA knockdown of Galectin-9 was co-cultured with T cells in vitro. Immunofluorescence and Western blot verified that PRDX2 regulates Galectin-9 expression through HDAC3 . Results PRDX2 expression was negatively correlated with CD8+ T cell expression in LUAD patients. Inhibition of PRDX2 significantly enhanced T-cell killing of LUAD cells and reduced tumor load in both in vitro and in vivo models. Mechanistically, Conoidin A or shRNA_PRDX2 decreased Galectin-9 expression by down-regulating the phosphorylation of HDAC3, consequently enhancing the infiltration and function of CD8+ T cells. Conclusions This study reveals the role of the PRDX2/HDAC3/Galectin-9 axis in LUAD immune escape and indicates Galectin-9 as a promising target for immunotherapy. Keywords PRDX2, Lung adenocarcinoma, HDAC3, Galectin-9, Immune checkpoint †Anqi Cheng: Co-first author. *Correspondence: Dong Hu[dhu@aust.edu.cn](dhu@aust.edu.cn)[ ](dhu@aust.edu.cn)Jing Wu [aust_jingwu@aust.edu.cn](aust_jingwu@aust.edu.cn) 1School of Medicine, Anhui University of Science and Technology, Huainan, Anhui 232000, China 2Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui 232000, China 3Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, Anhui 232000, China 4Joint Research Center for Occupational Medicine and Health of IHM, School of Medicine, Anhui University of Science and Technology, Huainan, Anhui 232000, China 5The First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital, School of Medicine), Huainan, Anhui 232000, China 6Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 232001, China © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons lice

FAQs

What is the main question addressed by the study?

How PRDX2 influences T cells in the lung adenocarcinoma tumor immune microenvironment and which immune-related target mediates tumor immune escape.

Which mechanistic axis is investigated?

The PRDX2/HDAC3/Galectin-9 axis, focusing on how PRDX2 regulates Galectin-9 expression through HDAC3.

What outcomes are observed when PRDX2 is inhibited?

PRDX2 inhibition enhances CD8+ T cell killing of lung adenocarcinoma cells and reduces tumor burden in both in vitro and in vivo models.

Sep 24, 2026

Uploaded by Margaret