2. Academic Validation
  3. Synergistic reprogramming of the tumor immune microenvironment by Senecavirus A and STING agonist

Synergistic reprogramming of the tumor immune microenvironment by Senecavirus A and STING agonist

  • Oncogene. 2026 Mar;45(9):809-822. doi: 10.1038/s41388-026-03685-0.
Xiaoya Zhao # 1,  Long Gao # 1,  Ran Chen 2 3,  Hanchen Tian 1,  Shuangshuang Liang 1,  Zhuofan Zhang 1,  Wenjie Li 1,  Jingshuai Sun 1,  Xuemei Chen 1,  Xiaoyu Tang 1,  Tian Lan 1,  Yuan Sun 4,  Jingyun Ma 5 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China.
  • 2 Center for Clinical Research and Translational Medicine, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 3 Department of General Surgery, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 4 State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China. [email protected].
  • 5 State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China. [email protected].
  • 6 Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong, China. [email protected].
  • # Contributed equally.
PMID: 41673092 DOI: 10.1038/s41388-026-03685-0
Abstract

Stimulator of interferon genes (STING) agonists have shown promise in Cancer Immunotherapy by enhancing type I interferon (IFN-I) signaling. However, the Antiviral effects of IFN-I can suppress viral replication, limiting their combination with oncolytic viruses. This study demonstrates that combining a naturally isolated Senecavirus A (SVA) strain with the STING agonist MSA-2 supports synergistic IFN-I activation across multiple tumor models. The combination induces robust innate and adaptive antitumor immune responses without impairing SVA replication. Transcriptomics, immunoblotting and early IRF7 nuclear translocation in B16‑F10 cells are consistent with engagement of the RIG‑I/MDA5-TBK1-IRF7 axis. In vivo, co‑treatment enhanced IFN‑β induction, increased CD8⁺ T‑cell infiltration and reduced tumor burden relative to monotherapies, whereas efficacy was not observed in athymic nude mice, supporting T‑cell dependence. Together, these data provide preclinical evidence that a rational oncolytic virus and STING combination can amplify antitumor immunity without overtly compromising viral persistence.

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