Combined targeting of CCL7 and Flt3L to promote the expansion and infiltration of cDC1s in tumors enhances T-cell activation and anti-PD-1 therapy effectiveness in NSCLC  

作　　者：Hong-Peng Dong Ying Li Zhen Tang Peng Wang Bo Zhong Qian Chu Dandan Lin 

机构地区：[1]Cancer Center,Renmin Hospital of Wuhan University,Medical Research Institute and Frontier Science Center of Immunology and Metabolism,Wuhan University,Wuhan 430071,China [2]College of Life Sciences,Wuhan University,Wuhan 430072,China [3]CAS Key Laboratory of Infection and Immunity,Institute of Biophysics,Chinese Academy of Sciences,Beijing 10011,China [4]Taikang Center for Life and Medical Sciences,Wuhan University,Wuhan 430071,China [5]Department of Oncoogy,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Cellular & Molecular Immunology》2023年第7期850-853,共4页中国免疫学杂志（英文版）

基　　金：the National Key Research and Development Program of China(2022YFC3401500);the Natural Science Foundation of China(31930040,32070900,and32270951);the Fundamental Research Funds for the Central Universities(2042022kf1187).

摘　　要：mmune checkpoint inhibitors(ICIs),represented by anti-PD-1/PD-L1 antibodies,have been widely applied in various cancers,and the efficacy of ICIs is closely associated with the tumor immune microenvironment(TIME)[1,2].We previously demonstrated that the alveolar macrophage-derived chemokine CCL7 recruited conventional type 1 dendritic cells(cDC1s)to remodel the TIME,thereby promoting the expansion of T cells to inhibit non-small cell lung cancer(NSCLC)progression in KrasLSL-G12D/+Tp53fl/fl(KP)and KrasLSL-G12D/+Lkb1fl/fl(KL)mouse models[3].Here,we showed that the fusion protein PD-1Ab7,in which CCL7 was fused with the single-chain variable fragment region(scFv)of an anti-PD-1 antibody(PD-1Ab),exhibited antitumor activity superior to that of PD-1Ab in a manner dependent on cDC1s.In addition,Fms-like tyrosine kinase 3 ligand(Flt3L)synergized with PD-1Ab7 to inhibit NSCLC progression in both the KP and the KL mouse models.Mechanistically,Flt3L promoted the generation and proliferation of cDC1s,whereas PD-1Ab7 increased the infiltration and migration of cDC1s in the TIME to potentiate the activation and proliferation of T cells.These findings not only highlight the essential roles of the PD-1Ab-based chemokine fusion strategy in targeting cDC1s and T cells to potentiate the efficacy of ICIs for cancer prevention but also provide therapeutic lead molecules for antitumor therapy.

关 键 词：FLT3L NSCLC prevention 

分 类 号：R730.51[医药卫生—肿瘤]