增强抗 PD-L1 抗体联合安罗替尼疗效，源于肿瘤微脉管内皮 PD-L1 的下调：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.
机构信息
Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China.
出版信息
Cancer Biol Med. 2024 May 29;21(10):951-62. doi: 10.20892/j.issn.2095-3941.2023.0423.
OBJECTIVE
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.
METHODS
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.
RESULTS
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) = 0.390 (95% confidence interval {CI}, 0.201-0.756), = 0.005; HR = 0.397 (0.208-0.756), = 0.005]. The results were similar among 58 patients with high PD-L1 expression in LECs and TCs [159 and 209 82 days, HR = 0.445 (0.210-0.939), = 0.034; HR = 0.369 (0.174-0.784), = 0.009], and 53 patients with high PD-L1 expression in BECs and TCs [161 and 209 41 days, HR = 0.340 (0.156-0.742), = 0.007; HR = 0.340 (0.159-0.727), = 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.
CONCLUSIONS
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.
目的
确定安罗替尼对程序性死亡受体配体（PD-L1）抗体的可能增强作用，以及微脉管内皮细胞（包括淋巴管内皮细胞[LECs]和血内皮细胞[BECs]）中 PD-L1 的疗效预测能力，以确定哪些患者将从这种治疗中受益。
方法
在非小细胞肺癌患者的 TQB2450（PD-L1 抗体）单药或联合安罗替尼的研究者手册临床试验中，使用多色免疫荧光法在石蜡切片上评估 LECs、BECs 和肿瘤细胞（TCs）中的 PD-L1 阳性率。比较两组之间不同 PD-L1 表达水平的无进展生存期（PFS）。
结果
在 75 例患者中，接受 TQB2450 联合安罗替尼治疗的患者 [10 和 12 mg（分别为 161 和 194 天）]的中位 PFS（mPFS）长于接受 TQB2450 单药治疗的患者（61 天）[风险比（HR）=0.390（95%置信区间[CI]，0.201-0.756）， = 0.005；HR=0.397（0.208-0.756）， = 0.005]。在 LECs 和 TCs 中高 PD-L1 表达的 58 例患者 [159 和 209 82 天，HR=0.445（0.210-0.939）， = 0.034；HR=0.369（0.174-0.784）， = 0.009]和 LECs 和 TCs 中高 PD-L1 表达的 53 例患者 [161 和 209 41 天，HR=0.340（0.156-0.742）， = 0.007；HR=0.340（0.159-0.727）， = 0.005]中，也观察到 mPFS 存在相似的结果。在 13 例低/无 LEC 表达和 18 例低/无 BEC 表达 PD-L1 病例中，TQB2450 组与联合治疗组之间 mPFS 无差异。
结论
在 LECs 和/或 BECs 中 PD-L1 高表达的患者中，单免疫治疗无效。安罗替尼可能通过下调 LECs 和/或 BECs 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人群的一种可行标志物。
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