A critical function for type I interferons in cancer immunoediting.
'Cancer immunoediting' is a process wherein the immune system protects hosts against tumor development and facilitates outgrowth of tumors with reduced immunogenicity. Although interferon-gamma (IFN-gamma) is known to be involved in this process, the involvement of type I interferons (IFN-alpha/beta) has not been elucidated. We now show that, like IFN-gamma, endogenously produced IFN-alpha/beta was required for the prevention of the growth of primary carcinogen-induced and transplantable tumors. Although tumor cells are important IFN-gamma targets, they are not functionally relevant sites of the actions of the type I interferons. Instead, host hematopoietic cells are critical IFN-alpha/beta targets during development of protective antitumor responses. Therefore, type I interferons are important components of the cancer immunoediting process and function in a way that does not completely overlap the functions of IFN-gamma.
Dunn
Gavin P
GP
Department of Pathology and Immunology, Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Bruce
Allen T
AT
Sheehan
Kathleen C F
KC
Shankaran
Vijay
V
Uppaluri
Ravindra
R
Bui
Jack D
JD
Diamond
Mark S
MS
Koebel
Catherine M
CM
Arthur
Cora
C
White
J Michael
JM
Schreiber
Robert D
RD
D000818:Animals; D004268:DNA-Binding Proteins / Q000276:immunology; D006410:Hematopoiesis / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D008748:Methylcholanthrene; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology*; D011828:Radiation Chimera; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000276:immunology*; D012509:Sarcoma / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology*
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D008565:Membrane Proteins; C499308:Rag2 protein, mouse; D017471:Receptors, Interferon; C064655:V(D)J recombination activating protein 2; D053633:Receptor, Interferon alpha-beta; D008748:Methylcholanthrene