Targeting HMGB2 acts as dual immunomodulator by bolstering CD8⁺ T cell function and inhibiting tumor growth in hepatocellular carcinoma.

ABSTRACT: T cell exhaustion is a critical obstacle for durable treatment response in hepatocellular carcinoma (HCC). Developing drugs that control tumor growth and simultaneously bolster immune function is of great significance. Although high-mobility group box 2 (HMGB2) has been reported to be crucial to HCC prognosis, its role in the tumor microenvironment remains unclear. Here, we found HMGB2⁺ CD8⁺ T cells as being associated with immune exhaustion and resistance to anti-PD-1 treatment through single-cell RNA sequencing. Mechanistically, HMGB2 impaired the oxidative phosphorylation in CD8⁺ T cells and inactivated the interferon-γ response in tumor cells, reducing the antitumor effector function. Tannic acid, a specific inhibitor of HMGB2, synergized with PD-1 anti

SUBMITTER: Qu WF 

PROVIDER: S-EPMC12047442 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature