识别外周血 (PB) 中与肿瘤相关的 T 细胞亚群已成为癌症治疗的潜在策略。然而，可用于治疗癌症的 PB 子集仍然不明确。在这里，我们发现，根据配对单细胞测定，肺癌患者血液中的 CX3CR1 T 细胞亚群表现出效应特性，并且与肿瘤浸润淋巴细胞 (TIL) 相比，与 CX3CR1-T 细胞相比具有更高的 TCR 匹配率。 RNA 和 TCR 测序。同时，CX3CR1 T 细胞的体外和体内抗肿瘤活性、效应细胞因子产生和线粒体功能均得到增强。然而，在H322细胞与T细胞的共培养体系中，CX3CR1 T细胞中凋亡细胞和Fas的百分比明显高于CX3CR1-T细胞。 Fas 介导的细胞凋亡通过抗 PD-1 抗体治疗得以挽救。因此，CX3CR1 T细胞的过继转移和抗PD-1治疗相结合显着降低了Fas表达并提高了肺异种移植小鼠的存活率。此外，PB 中 CX3CR1 T 细胞频率的增加与接受抗 PD-1 治疗的肺癌患者的更好反应和延长生存期相关。这些发现表明外周 CX3CR1 T 细胞过继转移作为个体癌症免疫疗法的巨大潜力。© 2024 作者。由泰勒授权出版

Identifying 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.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.