CD38 degrades MAVS through mitophagy to inhibit type I interferon secretion in nasopharyngeal carcinoma cells and impairs CD8+T cell-mediated anti-tumor immunity

  • Nat Commun. 2026 Feb 9;17(1):2544. doi: 10.1038/s41467-026-69339-7.
Lin Liang  1  2 ,  Wentao Li  2 ,  Siyi Liu  2 ,  Qian He  3 ,  Feng Zeng  2 ,  Jiaying Cao  2 ,  Yan Lei  4 ,  Yanling Li  5 ,  Yanhong Zhou  6  7
Affiliations
  • 1. Department of Nuclear Medicine, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital & Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 2. NHC Key Laboratory of Carcinogenesis, Cancer Research Institute, Basic School of Medicine, Central South University, Changsha, Hunan, China.
  • 3. Department of Radiation Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, China.
  • 4. Department of Blood Transfusion, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, China.
  • 5. Department of Nuclear Medicine, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital & Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China. [email protected].
  • 6. NHC Key Laboratory of Carcinogenesis, Cancer Research Institute, Basic School of Medicine, Central South University, Changsha, Hunan, China. [email protected].
  • 7. Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Basic School of Medicine, Central South University, Changsha, Hunan, China. [email protected].
PMID: 41663422 DOI: 10.1038/s41467-026-69339-7
Abstract

Activating the type I interferon response in tumor cells and enhancing T cell-mediated anti-tumor immunity have broad clinical applications in tumor immunotherapy. However, the detailed mechanisms underlying the antitumor immune response and type I interferon response in nasopharyngeal carcinoma (NPC) remain unclear and require further elucidation. In this study, we identify CD38 in NPC cells as a key mediator impairing T cell antitumor immunity. Mechanistically, CD38 induces mitochondrial Autophagy through PHB2, enhances the interaction between PHB2 and MAVS, leading to the degradation of MAVS protein, and inhibits the type I interferon response and CD8+T cell-mediated anti-tumor immunity. Importantly, CD38 promotes tumor progression and reduces the proportion of CD8+T cells and IFNγ+CD8+T cells in vivo via MAVS. In conclusion, these findings reveal previously unrecognized roles and mechanisms of CD38 in regulating anti-tumor T cell immunity, suggesting that inhibition of CD38 could initiate tumor-targeted immune responses, enhance anti-tumor immunity in patients, and provide new therapeutic strategies for NPC.

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