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Cancer Cell. 2014 Jan 13;25(1):37-48. doi: 10.1016/j.ccr.2013.12.004.

Targeting the tumor microenvironment with interferon-β bridges innate and adaptive immune responses.

Author information

1
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.
2
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.
3
Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
4
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.
5
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.
6
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.

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.

PMID:
24434209
PMCID:
PMC3927846
DOI:
10.1016/j.ccr.2013.12.004
[Indexed for MEDLINE]
Free PMC Article
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