Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan.
Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan.
Cancer Immunol Immunother. 2023 Aug;72(8):2829-2840. doi: 10.1007/s00262-023-03464-w. Epub 2023 May 16.
Immune checkpoint inhibitors (ICIs) have significantly improved the prognosis of non-small cell lung cancer (NSCLC). However, only a limited proportion of patients can benefit from this therapy, and clinically useful predictive biomarkers remain to be elucidated.
Blood was collected from 189 patients with NSCLC before and six weeks after the initiation of ICI treatment (anti-PD-1 or anti-PD-L1 antibody). Soluble PD-1 (sPD-1) and PD-L1 (sPD-L1) in plasma before and after treatment were analyzed to evaluate their clinical significance.
Cox regression analysis demonstrated that higher sPD-L1 levels before treatment significantly predicted unfavorable progression-free survival (PFS; HR 15.4, 95% CI 1.10-86.7, P = 0.009) and overall survival (OS; HR 11.4, 95% CI 1.19-52.3, P = 0.007) in NSCLC patients treated with ICI monotherapy (n = 122) but not in those treated with ICIs combined with chemotherapy (n = 67: P = 0.729 and P = 0.155, respectively). In addition, higher sPD-1 levels after treatment were significantly associated with better OS (HR 0.24, 95% CI 0.06-0.91, P = 0.037) in patients treated with anti-PD-1 monotherapy, whereas higher sPD-L1 levels after treatment were significantly associated with worse PFS (HR 6.09, 95% CI 1.42-21.0, P = 0.008) and OS (HR 42.6, 95% CI 6.83-226, P < 0.001). The levels of sPD-L1 at baseline closely correlated with those of other soluble factors, such as sCD30, IL-2Ra, sTNF-R1, and sTNF-R2, which are known to be released from the cell surface by zinc-binding proteases ADAM10/17.
These findings suggest the clinical significance of pretreatment sPD-L1 as well as posttreatment sPD-1 and sPD-L1 in NSCLC patients treated with ICI monotherapy.
免疫检查点抑制剂（ICIs）显著改善了非小细胞肺癌（NSCLC）的预后。然而，只有有限比例的患者能从中受益，且仍需要阐明有临床应用价值的预测生物标志物。
在开始 ICI 治疗（抗 PD-1 或抗 PD-L1 抗体）前和治疗后 6 周，收集了 189 名 NSCLC 患者的血液。分析了治疗前后血浆中可溶性 PD-1（sPD-1）和 PD-L1（sPD-L1）的水平，以评估其临床意义。
Cox 回归分析表明，治疗前 sPD-L1 水平较高显著预测 NSCLC 患者接受 ICI 单药治疗（n=122）无进展生存期（PFS；HR 15.4，95%CI 1.10-86.7，P=0.009）和总生存期（OS；HR 11.4，95%CI 1.19-52.3，P=0.007）较差，但在接受 ICI 联合化疗的患者（n=67：P=0.729 和 P=0.155）中则不然。此外，在接受抗 PD-1 单药治疗的患者中，治疗后 sPD-1 水平较高与 OS 较好显著相关（HR 0.24，95%CI 0.06-0.91，P=0.037），而治疗后 sPD-L1 水平较高与 PFS（HR 6.09，95%CI 1.42-21.0，P=0.008）和 OS（HR 42.6，95%CI 6.83-226，P<0.001）较差显著相关。基线时 sPD-L1 水平与其他可溶性因子（如 sCD30、IL-2Ra、sTNF-R1 和 sTNF-R2）的水平密切相关，这些因子已知通过锌结合蛋白酶 ADAM10/17 从细胞表面释放。
这些发现提示，在接受 ICI 单药治疗的 NSCLC 患者中，治疗前 sPD-L1 以及治疗后 sPD-1 和 sPD-L1 的水平具有临床意义。
