ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
GPX2+ Tumor Cells Recruit LGALS1+ B Cells via CCL26-CCR3 Axis to Promote Immunosuppression and Tumor Progression in Hepatocellular Carcinoma
Liang Lin 1
Shiye Yang 2
Jixiang Zhang 3
Guodu Chen 1
Wuhan Zhou 1
Dongxing Chen 1
Jiafei Chen 1
1. The First Hospital of Putian City, Putian, China
2. Nantong First People's Hospital, Nantong, China
3. Zhongshan City People's Hospital, Zhongshan, China
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Abstract
The molecular link between Hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) progression remains elusive. Here, we identify glutathione peroxidase 2 (GPX2) as a pivotal mediator of this process. Single-cell analysis of HBV-positive HCC reveals a distinct GPX2⁺ CSC population characterized by high MYC and CD44 expression. We demonstrate that GPX2 preserves stemness intrinsically by mitigating ROS-mediated c-MYC nuclear-cytoplasmic distribution, while extrinsically fostering immune evasion via the CCL26-CCR3 signaling axis. specifically, GPX2-derived CCL26 recruits and educates B cells towards an immunosuppressive LGALS1⁺ state, which predicts adverse patient outcomes. In vivo, GPX2 overexpression accelerates tumorigenesis, whereas targeting CCR3 with ALK4290 sensitizes tumors to anti-PD-1 checkpoint blockade. These findings delineate a dual mechanism whereby GPX2 couples oxidative stress regulation to immune modulation, positioning the GPX2-B cell axis as a promising therapeutic target for HBV-driven liver cancer.
Summary
Keywords
B cell, CSCs, GPX2, HBV-positive HCC, ROS
Received
21 September 2025
Accepted
19 February 2026
Copyright
© 2026 Lin, Yang, Zhang, Chen, Zhou, Chen and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jiafei Chen
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