Autologous Peripheral Vγ9Vδ2 T Cell Synergizes with αβ T Cell Through Antigen Presentation and BTN3A1 Blockade in Immunotherapy of Cervical Cancer
New treatment strategies are urgently needed for patients with advanced cervical cancer (CC). Here, a synergistic anti-CC effect of a novel combinatorial immunotherapy with adoptively transferred autologous Vγ9Vδ2 T cells and αβ T cells is shown. The pivotal role of both circulating and tumor-infiltrating Vγ9Vδ2 T cells in anti-CC immunity is uncovered. Importantly, autologous Vγ9Vδ2 T cells show a synergistic anti-CC effect with αβ T cells not only through killing tumor directly, but also by promoting the activation and tumoricidal activity of syngeneic αβ T cells through antigen presentation, which can be further boosted by conventional chemotherapy. Moreover, Vγ9Vδ2 T cells can restore the tumoricidal function of αβ T cell through competitively binding to BTN3A1, a TCR-Vγ9Vδ2 ligand on CC cells upregulated by IFN-γ derived from activated αβ T cell. These findings uncover a critical synergistic effect of autologous Vγ9Vδ2 T cells and αβ T cells in immunotherapy of CC and reveal the underlying mechanisms.
Authors
- Junyan Han (ORCID: https://orcid.org/0000-0002-5266-033X)
- Shuo Yuan
- Min Wu (ORCID: https://orcid.org/0009-0003-1339-6016)
- Yafei Huang (ORCID: https://orcid.org/0000-0002-1711-2354)
- Shen Qu (ORCID: https://orcid.org/0000-0003-0811-7070)
- Yifan Yang (ORCID: https://orcid.org/0000-0001-9127-168X)
- Ying Chen (ORCID: https://orcid.org/0000-0001-5833-2380)
- Liming Wang (ORCID: https://orcid.org/0000-0003-3354-2079)
- Hong Liu (ORCID: https://orcid.org/0000-0003-4488-0372)
- Jingyu Wang (ORCID: https://orcid.org/0000-0003-0218-8978)
- Ling Feng (ORCID: https://orcid.org/0000-0001-8833-5574)
- Hui Wang (ORCID: https://orcid.org/0000-0001-6789-5185)
- Shan He (ORCID: https://orcid.org/0000-0002-8558-7490)
- Wanjiang Zeng
- Haihong Zeng
- Han Jiang (ORCID: https://orcid.org/0009-0009-6200-2742)
- Li‐Ting Liu (ORCID: https://orcid.org/0000-0002-7641-4774)
- Jian Liu (ORCID: https://orcid.org/0000-0002-6048-9333)
- Hangyu Liu
- Yu Long
- Ruiyi Xu
- Yuwei Zhang (ORCID: https://orcid.org/0009-0008-1016-7361)
Institutions
- Women's Hospital, School of Medicine, Zhejiang University (CN)
- Tongji Hospital (CN)
- Huazhong University of Science and Technology (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-03-17
- DOI
- https://doi.org/10.1002/advs.202401230
- Citations
- 2
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China