首页|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

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

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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 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.

PD-L1lymphatic endothelial cellblood endothelial cellanlotinibprogression-free survival

Cuicui Zhang、Tianqing Chu、Qiming Wang、Ying Cheng、Yongxiang Zhang、Ruili Wang、Leilei Ma、Chaonan Qian、Baohui Han、Kai Li

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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

Department of Internal Medicine,Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Zhengzhou 450003,China

Department of Thoracic Medical Oncology,Jilin Cancer Hospital,Changchun 130012,China

Department of Respiratory&Critical Care Medicine,Tianjin Chest Hospital,Tianjin 300222,China

Panovue Biotechnology(Beijing)Co.,Ltd,Beijing 100096,China

Medical Affairs Department,Chia-Tai Tian Qing Pharmaceutical Co.,Ltd.,Nanjing 210046,China

Department of Radiation Oncology,Guangzhou Concord Cancer Center,Guangzhou 510555,China

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2024

10.20892/j.issn.2095-3941.2023.0423

癌症生物学与医学(英文版)
中国抗癌协会

癌症生物学与医学(英文版)

CSTPCD
影响因子：1.07
ISSN：2095-3941
年,卷(期)：2024.21(10)