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J Exp Med. 2012 Sep 24;209(10):1869-82. Epub 2012 Aug 27.

Cancer immunoediting by the innate immune system in the absence of adaptive immunity.

Author information

1
Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA.

Abstract

Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3'methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2(-/-), and RAG2(-/-)x γc(-/-) mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2(-/-)x γc(-/-) mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting.

PMID:
22927549
PMCID:
PMC3457735
DOI:
10.1084/jem.20112738
[Indexed for MEDLINE]
Free PMC Article

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