Authors: Min Wu, Jian Liu, Liting Liu, Yifan Yang, Hong Liu, Long Yu, Haihong Zeng, Shuo Yuan, Ruiyi Xu, Hangyu Liu, Han Jiang, Shen Qu, Liming Wang, Ying Chen, Jingyu Wang, Yuwei Zhang, Shan He, Ling Feng, Junyan Han, Wanjiang Zeng, Hui Wang, Yafei Huang
Published: 2025-03-17
Source: Full article
AbstractNew 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.