Costantini Adrien, Takam Kamga Paul, Pons-Tostivint Elvire, Fradin Delphine, Emile Jean-François, Giroux-Leprieur Etienne
Department of Respiratory Diseases and Thoracic Oncology, Cancer Institute APHP. Paris-Saclay University, Hôpital Ambroise Paré, 9 Avenue Charles de Gaulle, 92100, Boulogne-Billancourt, France.
EA 4340 BECCOH, Université Paris-Saclay-UVSQ, 9 Avenue Charles de Gaulle, 92100, Boulogne-Billancourt, France.
Cancer Immunol Immunother. 2025 Aug 26;74(9):294. doi: 10.1007/s00262-025-04126-9.
There is a need for biomarkers to predict response and survival to immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Soluble PD-L1 (sPD-L1) has shown biomarker potential. The objective of this study was to evaluate sPD-L1 in patients with advanced NSCLC treated with first-line ICIs.
We constructed three prospective cohorts of patients with advanced NSCLC treated with first-line chemotherapy (CT), (Cohort #1), ICIs, or CT-ICIs (Cohort #2 and #3). Plasma was collected at baseline and at first tumour evaluation. sPD-L1 levels were measured by ELISA and compared to response and survival metrics.
Patients were mostly male smokers with adenocarcinomas. Baseline sPD-L1 was lower in responders versus (vs) non-responders in Cohort #2 (p = 0.0233). Patients with low baseline sPD-L1 had longer OS in Cohorts #2 and #3: median OS 18.0 months vs 4.0 months, (p = 0.0277) and not reached (NR) vs 13.0 months (p = 0.0360). First tumour evaluation sPD-L1 was lower in responders in Cohorts #1 (p = 0.0138) and #2 (p = 0.0009). Patients with low sPD-L1 at first tumour evaluation had longer OS in Cohort #2: 45.0 months vs 12.5 (p = 0.0041). Patients with stable/decreasing sPD-L1 had longer OS throughout the Cohorts: median OS of 15.5 vs 6.0 months, 45.0 vs 14.0 months and not reached (NR) vs 17.0 months in Cohorts #1, #2 and #3. In vitro studies confirmed that cancer and immune cells secreted sPD-L1 and that NSLC patient plasma has the capacity to inhibit lymphocyte proliferation.
sPD-L1 has prominent biomarker potential in advanced NSCLC treated with first-line ICIs.
晚期非小细胞肺癌（NSCLC）患者需要生物标志物来预测对免疫检查点抑制剂（ICI）的反应和生存期。可溶性程序性死亡配体1（sPD-L1）已显示出作为生物标志物的潜力。本研究的目的是评估一线ICI治疗的晚期NSCLC患者的sPD-L1水平。
我们构建了三个前瞻性队列，分别为接受一线化疗（CT）的晚期NSCLC患者（队列1）、接受ICI治疗的患者以及接受CT-ICI联合治疗的患者（队列2和队列3）。在基线和首次肿瘤评估时采集血浆。通过酶联免疫吸附测定（ELISA）法检测sPD-L1水平，并与反应和生存指标进行比较。
患者大多为男性吸烟者，患有腺癌。队列2中，反应者的基线sPD-L1低于无反应者（p = 0.0233）。队列2和队列3中，基线sPD-L1水平低的患者总生存期更长：中位总生存期分别为18.0个月和4.0个月（p = 0.0277），未达到（NR）和13.0个月（p = 0.0360）。队列1（p = 0.0138）和队列2（p = 0.0009）中，反应者的首次肿瘤评估时sPD-L1水平较低。队列2中，首次肿瘤评估时sPD-L1水平低的患者总生存期更长：45.0个月和12.5个月（p = 0.0041）。在所有队列中，sPD-L1稳定/下降的患者总生存期更长：队列1、队列2和队列3的中位总生存期分别为15.5个月和6.0个月、45.0个月和14.0个月、未达到（NR）和17.0个月。体外研究证实，癌症细胞和免疫细胞可分泌sPD-L1，且NSCLC患者血浆具有抑制淋巴细胞增殖的能力。
sPD-L1在一线ICI治疗的晚期NSCLC中具有显著的生物标志物潜力。
