Department of Radiology, Sapporo Medical University, Sapporo, Japan.
Department of Pathology, Sapporo Medical University, Sapporo, Japan.
Cancer Sci. 2022 Dec;113(12):4394-4400. doi: 10.1111/cas.15566. Epub 2022 Sep 21.
Combined chemoradiotherapy (CRT) and programmed cell death-ligand 1 (PD-L1) blockade is a new care standard for unresectable stage III non-small-cell lung cancer (NSCLC). Although this consolidation therapy has improved the overall survival of patients with NSCLC, the synergistic action mechanisms of CRT and immunotherapy on T cells remain unclear. In addition, there is a paucity of reliable biomarkers to predict clinical responses to therapy. In this study, we analyzed T-cell receptor (TCR) sequences in the peripheral blood of five patients with NSCLC. T-cell receptor analysis was undertaken before treatment, after CRT, and after PD-L1 blockade. Notably, we observed the expansion and alteration of the dominant T-cell clonotypes in all cases with a complete response. In contrast, neither expansion nor alteration of the TCR repertoire was observed in cases with progressive disease. T cell expansion was initiated after CRT and was further enhanced after PD-L1 blockade. Our findings suggest the systemic effect of CRT on circulating T cells in addition to the curative effect on limited tumor sites. Dynamic changes in circulating T-cell clonotypes could have a prognostic significance for combined CRT and PD-L1 blockade.
联合放化疗（CRT）和程序性细胞死亡配体 1（PD-L1）阻断是不可切除的 III 期非小细胞肺癌（NSCLC）的新治疗标准。尽管这种巩固治疗改善了 NSCLC 患者的总生存期，但 CRT 和免疫疗法对 T 细胞的协同作用机制仍不清楚。此外，缺乏可靠的生物标志物来预测对治疗的临床反应。在这项研究中，我们分析了 5 名 NSCLC 患者外周血中的 T 细胞受体（TCR）序列。在治疗前、CRT 后和 PD-L1 阻断后进行 T 细胞受体分析。值得注意的是，我们观察到所有完全缓解患者的优势 T 细胞克隆型都出现了扩增和改变。相比之下，进展性疾病患者既没有观察到 TCR 库的扩增，也没有观察到其改变。T 细胞扩增始于 CRT 之后，并在 PD-L1 阻断后进一步增强。我们的研究结果表明，CRT 对循环 T 细胞的全身性作用，除了对有限的肿瘤部位的疗效之外。循环 T 细胞克隆型的动态变化可能对联合 CRT 和 PD-L1 阻断具有预后意义。
