期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 208, 期 10, 页码 1989-2003出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20101158
关键词
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资金
- National Cancer Institute, National Institute of Allergy and Infectious Diseases (NIAID
- Midwest Regional Center of Excellence)
- National Institute of Arthritis and Musculoskeletal and Skin Disease (Rheumatic Disease Core Centers)
- Cancer Research Institute
- Ludwig Institute for Cancer Research
- NIAID
Cancer immunoediting is the process whereby the immune system suppresses neoplastic growth and shapes tumor immunogenicity. We previously reported that type I interferon (IFN-alpha/beta) plays a central role in this process and that hematopoietic cells represent critical targets of type I IFN's actions. However, the specific cells affected by IFN-alpha/beta and the functional processes that type I IFN induces remain undefined. Herein, we show that type I IFN is required to initiate the antitumor response and that its actions are temporally distinct from IFN-gamma during cancer immunoediting. Using mixed bone marrow chimeric mice, we demonstrate that type I IFN sensitivity selectively within the innate immune compartment is essential for tumor-specific T cell priming and tumor elimination. We further show that mice lacking IFNAR1 (IFN-alpha/beta receptor 1) in dendritic cells (DCs; Itgax-Cre(+)Ifnar1(f/f) mice) cannot reject highly immunogenic tumor cells and that CD8 alpha(+) DCs from these mice display defects in antigen cross-presentation to CD8(+) T cells. In contrast, mice depleted of NK cells or mice that lack IFNAR1 in granulocytes and macrophage populations reject these tumors normally. Thus, DCs and specifically CD8 alpha(+) DCs are functionally relevant targets of endogenous type I IFN during lymphocyte-mediated tumor rejection.
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