1. Peripheral CX3CR1+ T cells combined with PD-1 blockade therapy potentiates the anti-tumor efficacy for lung cancer
- Author
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Congcong Li, Zhen Zhang, Qianfeng Cai, Qitai Zhao, Han Wu, JunRu Li, Yaqing Liu, Xuan Zhao, Jinyan Liu, Yu Ping, Jiqi Shan, Shengli Yang, and Yi Zhang
- Subjects
anti-PD-1 treatment ,cancer immunotherapy ,CX3CR1+ T cells ,Fas ,lung cancer ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ABSTRACTIdentifying tumor-relevant T cell subsets in the peripheral blood (PB) has become a potential strategy for cancer treatment. However, the subset of PB that could be used to treat cancer remains poorly defined. Here, we found that the CX3CR1+ T cell subset in the blood of patients with lung cancer exhibited effector properties and had a higher TCR matching ratio with tumor-infiltrating lymphocytes (TILs) compared to CX3CR1− T cells, as determined by paired single-cell RNA and TCR sequencing. Meanwhile, the anti-tumor activities, effector cytokine production, and mitochondrial function were enhanced in CX3CR1+ T cells both in vitro and in vivo. However, in the co-culture system of H322 cells with T cells, the percentages of apoptotic cells and Fas were substantially higher in CX3CR1+ T cells than those in CX3CR1− T cells. Fas-mediated apoptosis was rescued by treatment with an anti-PD-1 antibody. Accordingly, the combination of adoptive transfer of CX3CR1+ T cells and anti-PD-1 treatment considerably decreased Fas expression and improved the survival of lung xenograft mice. Moreover, an increased frequency of CX3CR1+ T cells in the PB correlated with a better response and prolonged survival of patients with lung cancer who received anti-PD-1 therapy. These findings indicate the promising potential of adoptive transfer of peripheral CX3CR1+ T cells as an individual cancer immunotherapy.
- Published
- 2024
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