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 Chaonan Qian Baohui Han Kai Li 

机构地区：[1]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 [2]Department of Respiratory Medicine,Shanghai Chest Hospital,Shanghai Jiaotong University,Shanghai 200030,China [3]Department of Internal Medicine,Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Zhengzhou 450003,China [4]Department of Thoracic Medical Oncology,Jilin Cancer Hospital,Changchun 130012,China [5]Department of Respiratory&Critical Care Medicine,Tianjin Chest Hospital,Tianjin 300222,China [6]Panovue Biotechnology(Beijing)Co.,Ltd,Beijing 100096,China [7]Medical Affairs Department,Chia-Tai Tian Qing Pharmaceutical Co.,Ltd.,Nanjing 210046,China [8]Department of Radiation Oncology,Guangzhou Concord Cancer Center,Guangzhou 510555,China

出　　处：《Cancer Biology & Medicine》2024年第10期951-962,共12页癌症生物学与医学（英文版）

摘　　要：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;HR_(12 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,HR_(10 mg)=0.445(0.210–0.939),P=0.034;HR_(12 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,HR_(10 mg)=0.340(0.156–0.742),P=0.007;HR_(12 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.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.

关 键 词：PD-L1 lymphatic endothelial cell blood endothelial cell anlotinib progression-free survival 

分 类 号：R734.2[医药卫生—肿瘤]