title: Targeting the tumor microenvironment with interferon-β bridges innate and adaptive immune responses.
abstract: Antibodies (Abs) that preferentially target oncogenic receptors have been increasingly used for cancer therapy, but tumors often acquire intrinsic Ab resistance after prolonged and costly treatment. Herein we armed the Ab with IFNβ and observed that it is more potent than the first generation of Ab for controlling Ab-resistant tumors. This strategy controls Ab resistance by rebridging suppressed innate and adaptive immunity in the tumor microenvironment. Mechanistically, Ab-IFNβ therapy primarily and directly targets intratumoral dendritic cells, which reactivate CTL by increasing antigen cross-presentation within the tumor microenvironment. Additionally, blocking PD-L1, which is induced by Ab-IFNβ treatment, overcomes treatment-acquired resistance and completely eradicates established tumors. This study establishes a next-generation Ab-based immunotherapy that targets and eradicates established Ab-resistant tumors.
authors.affiliation: IBP-UC Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Xuanming
authors.initials: X
authors.lastname: Yang
authors.affiliation: IBP-UC Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; International Joint Cancer Institute, The Second Military Medical University, New Library Building West 10(th)-11(th) Floor, 800 Xiang Yin Road, Shanghai 200433, China.
authors.forename: Xunmin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: May Lynne
authors.initials: ML
authors.lastname: Fu
authors.affiliation: Department of Radiation and Cellular Oncology, The Ludwig Center for Metastasis Research, University of Chicago, 5758 South Maryland Avenue MC 9006, Chicago, IL 60637, USA.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.affiliation: Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, New Library Building West 10(th)-11(th) Floor, 800 Xiang Yin Road, Shanghai 200433, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo
authors.affiliation: IBP-UC Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA. Electronic address: yfu@uchicago.edu.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D060890:B7-H1 Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D016899:Interferon-beta / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D000906:Antibodies; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D016899:Interferon-beta; C541485:EGFR protein, mouse; D066246:ErbB Receptors