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

  • Cancer Immunol Immunother. 2025 Aug 25;74(9):293. doi: 10.1007/s00262-025-04150-9.
Jingjing Wu  #  1  2  3 ,  Yuan Deng  #  2 ,  Yong Gao  4  5  6 ,  Bin Wei  7  8  9
Affiliations
  • 1. Department of Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
  • 2. Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
  • 3. Department of Oncology, The Huaian Clinical College of Xuzhou Medical University, Huai'an, China.
  • 4. Department of Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China. [email protected].
  • 5. Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University, Huai'an, China. [email protected].
  • 6. Department of Oncology, The Huaian Clinical College of Xuzhou Medical University, Huai'an, China. [email protected].
  • 7. Department of Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China. [email protected].
  • 8. Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University, Huai'an, China. [email protected].
  • 9. Department of Oncology, The Huaian Clinical College of Xuzhou Medical University, Huai'an, China. [email protected].
  • # Contributed equally.
PMID: 40853486 DOI: 10.1007/s00262-025-04150-9
Abstract

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.

Keywords
Anti-tumor immunity; Cell growth; Diffuse large B-cell lymphoma; Mitochondrial damage; PANoptosis; Spautin-1.
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