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

作者：Cuicui Zhang, Tianqing Chu, Qiming Wang, Ying Cheng, Yongxiang Zhang, Ruili Wang, Leilei Ma, Chao‐Nan Qian, Baohui Han, Kai Li · 发表于：Cancer Biology and Medicine · 年份：2024 · DOI：10.20892/j.issn.2095-3941.2023.0423 · 被引用次数：6 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Research Studies、Colorectal and Anal Carcinomas

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)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 TQB2...