外周 CX3CR1(+) T 细胞联合 PD-1 阻断治疗增强了肺癌的抗肿瘤疗效

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.