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 

作者机构：Cancer CenterRenmin Hospital of Wuhan UniversityMedical Research Institute and Frontier Science Center of Immunology and MetabolismWuhan UniversityWuhan 430071China College of Life SciencesWuhan UniversityWuhan 430072China CAS Key Laboratory of Infection and ImmunityInstitute of BiophysicsChinese Academy of SciencesBeijing 10011China Taikang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Department of OncoogyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2023年第20卷第7期

页      面：850-853页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

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) 

主　　题：Flt3L NSCLC prevention 

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 *** addition,Fms-like tyrosine kinase 3 ligand(Flt3L)synergized with PD-1Ab7 to inhibit NSCLC progression in both the KP and the KL mouse ***,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 *** 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.