CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors  

作　　者：Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao 

机构地区：[1]Department of Immunology,Leiden University Medical Center,Leiden,The Netherlands [2]Oncode Institute,Leiden University Medical Center,Leiden,The Netherlands [3]Department of Tumor Biology and Immunology,The Netherlands Cancer Institute,Amsterdam,The Netherlands [4]Department of Medical Oncology,Oncode Institute,Leiden University Medical Center,Leiden,The Netherlands [5]IMMIOS B.V.,Oss,The Netherlands [6]Division of Medical Oncology,The Netherlands Cancer Institute,Amsterdam,The Netherlands [7]Department of Otorhinolaryngology Leiden University Medical Center,Leiden,The Netherlands [8]Department of Pathology,Leiden University Medical Center,Leiden,The Netherlands

出　　处：《Cellular & Molecular Immunology》2024年第4期374-392,共19页中国免疫学杂志（英文版）

摘　　要：CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse models.We recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy.Here,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in humans.Activated CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses.In cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response induction.IFN-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T cells.In agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关 键 词：CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control 

分 类 号：R392[医药卫生—免疫学]