1. Cancer immunoediting by the innate immune system in the absence of adaptive immunity
- Author
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O’Sullivan, Timothy, Saddawi-Konefka, Robert, Vermi, William, Koebel, Catherine M, Arthur, Cora, White, J Michael, Uppaluri, Ravi, Andrews, Daniel M, Ngiow, Shin Foong, Teng, Michele WL, Smyth, Mark J, Schreiber, Robert D, and Bui, Jack D
- Subjects
Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Adaptive Immunity ,Animals ,CD40 Antigens ,Cell Line ,Tumor ,DNA-Binding Proteins ,Genetic Predisposition to Disease ,Histocompatibility Antigens Class II ,Immunity ,Innate ,Immunomodulation ,Interferon-gamma ,Interleukin Receptor Common gamma Subunit ,Killer Cells ,Natural ,Macrophages ,Mice ,Mice ,Knockout ,Neoplasms ,Phenotype ,Sarcoma ,Transplantation ,Isogeneic ,Medical and Health Sciences ,Immunology - 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.
- Published
- 2012