title: Cancer immunoediting by the innate immune system in the absence of adaptive immunity.
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.
authors.affiliation: Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Sullivan
authors.forename: Robert
authors.initials: R
authors.lastname: Saddawi-Konefka
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Koebel
authors.forename: Cora
authors.initials: C
authors.lastname: Arthur
authors.forename: J Michael
authors.initials: JM
authors.lastname: White
authors.forename: Ravi
authors.initials: R
authors.lastname: Uppaluri
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Andrews
authors.forename: Shin Foong
authors.initials: SF
authors.lastname: Ngiow
authors.forename: Michele W L
authors.initials: MW
authors.lastname: Teng
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Robert D
authors.initials: RD
authors.lastname: Schreiber
authors.forename: Jack D
authors.initials: JD
authors.lastname: Bui
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D019013:CD40 Antigens / Q000819:agonists; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007113:Immunity, Innate; D056747:Immunomodulation; D007371:Interferon-gamma / Q000096:biosynthesis; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D010641:Phenotype; D012509:Sarcoma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D014185:Transplantation, Isogeneic
chemical_list: D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D053631:Interleukin Receptor Common gamma Subunit; C499308:Rag2 protein, mouse; D007371:Interferon-gamma