Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806, Poznań, Poland.
Department of Clinical Oncology with the Subdepartment of Diurnal Chemotherapy, Wielkopolska Center of Pulmonology and Thoracic Surgery, 62 Szamarzewskiego Street, 60-569, Poznań, Poland.
Cancer Immunol Immunother. 2023 Jun;72(6):1853-1863. doi: 10.1007/s00262-023-03377-8. Epub 2023 Jan 23.
Immunotherapy has changed the paradigm of treating non-small cell lung cancer (NSCLC). But, selecting patients who will achieve long-term benefits from treatment remains unsatisfactory. Here, we investigated the possible use of the soluble form of CD8 antigen (sCD8) in predicting durable disease control after PD-1/PD-L1 blockade. CD8 is a marker of the cytotoxic T lymphocytes. Its soluble form (sCD8) is secreted under activation of the immune system but also has immunosuppressive properties. The data about serum sCD8 in patients dosed with anti-PD-1/PD-L1 drugs are lacking.
We included 42 NSCLC patients and collected samples at baseline and for the first 3 months of atezolizumab immunotherapy. The serum sCD8 concentrations were measured with the ELISA kit and correlated with treatment outcomes. Patients with durable (≥ 12 months) disease control presented lower serum sCD8 than those without long-term benefits. The sCD8 levels measured at the end of cycle 2 (sCD8.2) were the earliest time point that successfully differentiated patients (3.76 vs. 9.68 ng/mL, respectively, p < 0.001). Individuals with low sCD8.2 (≤ 4.09 ng/mL) presented longer progression-free survival (HR = 0.061, p < 0.001) and overall survival (HR = 0.104, p < 0.05) compared to individuals with high sCD8.2 (median values unreached vs. 4.4 months and 14.4 months for PFS and OS, respectively).
Serum sCD8 could be an early biomarker of durable disease control after anti-PD-L1 treatment. Higher sCD8 in patients with worse outcomes could suggest the inhibitory effect of sCD8 on cytotoxic T-cells activation.
免疫疗法改变了治疗非小细胞肺癌（NSCLC）的模式。但是，选择能够从治疗中获得长期获益的患者仍然不尽如人意。在这里，我们研究了可溶性 CD8 抗原（sCD8）在预测 PD-1/PD-L1 阻断后持久疾病控制中的可能用途。CD8 是细胞毒性 T 淋巴细胞的标志物。其可溶性形式（sCD8）在免疫系统激活时被分泌，但也具有免疫抑制特性。关于接受抗 PD-1/PD-L1 药物治疗的患者的血清 sCD8 数据尚缺乏。
我们纳入了 42 例 NSCLC 患者，并在接受阿特珠单抗免疫治疗的基线和前 3 个月采集了样本。使用 ELISA 试剂盒测量血清 sCD8 浓度，并将其与治疗结果相关联。具有持久（≥12 个月）疾病控制的患者的血清 sCD8 浓度低于无长期获益的患者。在第 2 个周期结束时测量的 sCD8（sCD8.2）是最早成功区分患者的时间点（分别为 3.76 和 9.68ng/mL，p<0.001）。sCD8.2 水平较低（≤4.09ng/mL）的患者的无进展生存期（HR=0.061，p<0.001）和总生存期（HR=0.104，p<0.05）均长于 sCD8.2 水平较高的患者（中位值未达到，分别为 4.4 个月和 14.4 个月）。
血清 sCD8 可能是抗 PD-L1 治疗后持久疾病控制的早期生物标志物。在结局较差的患者中 sCD8 水平较高可能表明 sCD8 对细胞毒性 T 细胞激活的抑制作用。
