由于肿瘤内微导管内皮细胞 PD-L1 的下调,抗 PD-L1 抗体加安罗替尼的疗效增强:一项随机双盲试验。
Enhancement of anti-PD-L1 antibody plus anlotinib efficacy due to downregulation of PD-L1 in the micro-conduit endothelium within the tumor: a randomized double-blind trial.
发表日期:2024 May 29
作者:
Cuicui Zhang, Tianqing Chu, Qiming Wang, Ying Cheng, Yongxiang Zhang, Ruili Wang, Leilei Ma, Chaonan Qian, Baohui Han, Kai Li
来源:
Cell Death & Disease
摘要:
确定了安罗替尼对程序性死亡受体配体(PD-L1)抗体可能的增强作用以及PD-L1在微导管内皮(包括淋巴内皮细胞(LEC)和血液内皮细胞(BEC))中的疗效预测能力以确定将从这种治疗中受益的患者。在单独或联合 TQB2450(PD-L1 抗体)的研究者手册临床试验中,使用带有多色免疫荧光的石蜡切片评估了 LEC、BEC 和肿瘤细胞 (TC) 中的 PD-L1 阳性情况。与安罗替尼联合治疗非小细胞肺癌患者。比较两组不同 PD-L1 表达水平的无进展生存期 (PFS)。 在 75 名患者中,接受 TQB2450 联合安罗替尼治疗的患者的中位 PFS (mPFS) 较长 [10 和 12 mg(161 和 194天)]比单独接受 TQB2450 的患者(61 天)[风险比 (HR)10 mg = 0.390(95% 置信区间 {CI},0.201-0.756),P = 0.005; HR12 毫克 = 0.397 (0.208-0.756),P = 0.005]。 58 例 LEC 和 TC 中 PD-L1 高表达的患者的结果相似 [159 和 209 vs. 82 天,HR10 mg = 0.445 (0.210-0.939),P = 0.034; HR12 mg = 0.369 (0.174-0.784),P = 0.009],以及 53 例 BEC 和 TC 中 PD-L1 高表达的患者[161 和 209 vs. 41 天,HR10 mg = 0.340 (0.156-0.742),P = 0.007 ; HR12 毫克 = 0.340 (0.159-0.727),P = 0.005]。在 13 例低/无 LEC 表达和 18 例低/无 BEC 表达 PD-L1 病例中,TQB2450 组和联合治疗组之间的 mPFS 没有检测到差异。单一免疫疗法对 PD-L1 高表达患者无效。 LEC 和/或 BEC。安罗替尼可以通过下调 LEC 和/或 BEC 中的 PD-L1 表达来提高疗效,这被认为是筛选接受抗血管生成治疗的最佳免疫患者群体的可行标志物。版权所有:© 2024,作者。
The possible enhancing effect of anlotinib on programmed death receptor ligand (PD-L1) antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium, including lymphatic endothelial cells (LECs) and blood endothelial cells (BECs), were determined to identify patients who would benefit from this treatment.PD-L1 positivity in LECs, BECs, and tumor cells (TCs) was assessed using paraffin sections with multicolor immunofluorescence in an investigator's brochure clinical trial of TQB2450 (PD-L1 antibody) alone or in combination with anlotinib in patients with non-small cell lung cancer. Progression-free survival (PFS) with different levels of PD-L1 expression was compared between the two groups.Among 75 patients, the median PFS (mPFS) was longer in patients who received TQB2450 with anlotinib [10 and 12 mg (161 and 194 days, respectively)] than patients receiving TQB2450 alone (61 days) [hazard ratio (HR)10 mg = 0.390 (95% confidence interval {CI}, 0.201-0.756), P = 0.005; HR12 mg = 0.397 (0.208-0.756), P = 0.005]. The results were similar among 58 patients with high PD-L1 expression in LECs and TCs [159 and 209 vs. 82 days, HR10 mg = 0.445 (0.210-0.939), P = 0.034; HR12 mg = 0.369 (0.174-0.784), P = 0.009], and 53 patients with high PD-L1 expression in BECs and TCs [161 and 209 vs. 41 days, HR10 mg = 0.340 (0.156-0.742), P = 0.007; HR12 mg = 0.340 (0.159-0.727), P = 0.005]. No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases.Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs. Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs, which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.Copyright: © 2024, The Authors.