Spautin-1 inhibits the growth of diffuse large B-cell lymphoma by inducing mitochondrial damage-mediated PANoptosis and anti-tumor immunity

作者：Jingjing Wu, Yuan Deng, Yong Gao, Bin Wei · 发表于：Cancer Immunology Immunotherapy · 年份：2025 · DOI：10.1007/s00262-025-04150-9 · 被引用次数：3 · 研究领域：Ubiquitin and proteasome pathways、Lymphoma Diagnosis and Treatment、Histone Deacetylase Inhibitors Research

The prognosis of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is poor. Therefore, searching for new therapeutic agents is particularly important to improve therapeutic efficacy. Targeting the ubiquitin-proteasome system is a potential therapeutic strategy for treating DLBCL. In this study, we investigated the role of the deubiquitase inhibitor Spautin-1 in the treatment of DLBCL. Spautin-1 significantly inhibited the growth of DLBCL, including the growth of cells and transplanted tumors in mice. Notably, Spautin-1 showed enhanced tumor suppression in immune-competent versus immunodeficient mice models, mediated by CD8 + T cell infiltration and activation. Mechanistically, Spautin-1 promotes PANoptosis by inducing mitochondrial damage mediated by USP13-ACLY inhibition in DLBCL cells, which in turn induces the release of injury-related molecular patterns and cytokines. Moreover, high USP13 expression in DLBCL is associated with poor prognosis and blocks CD8 + T cell infiltration. In summary, Spautin-1 may inhibit the growth of DLBCL cells by promoting mitochondrial damage-mediated PANoptosis and anti-tumor immunity, providing a potential strategy for DLBCL therapy.