IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity.
Lymphocytes were originally thought to form the basis of a 'cancer immunosurveillance' process that protects immunocompetent hosts against primary tumour development, but this idea was largely abandoned when no differences in primary tumour development were found between athymic nude mice and syngeneic wild-type mice. However, subsequent observations that nude mice do not completely lack functional T cells and that two components of the immune system-IFNgamma and perforin-help to prevent tumour formation in mice have led to renewed interest in a tumour-suppressor role for the immune response. Here we show that lymphocytes and IFNgamma collaborate to protect against development of carcinogen-induced sarcomas and spontaneous epithelial carcinomas and also to select for tumour cells with reduced immunogenicity. The immune response thus functions as an effective extrinsic tumour-suppressor system. However, this process also leads to the immunoselection of tumour cells that are more capable of surviving in an immunocompetent host, which explains the apparent paradox of tumour formation in immunologically intact individuals.
Shankaran
V
V
Department of Pathology and Immunology, Center for Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.
Ikeda
H
H
Bruce
A T
AT
White
J M
JM
Swanson
P E
PE
Old
L J
LJ
Schreiber
R D
RD
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology; D000818:Animals; D002277:Carcinoma / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D007121:Immunocompetence; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008748:Methylcholanthrene; D051379:Mice; D009368:Neoplasm Transplantation; D012190:Retroviridae / Q000302:isolation & purification; D012513:Sarcoma, Experimental / Q000276:immunology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; C499308:Rag2 protein, mouse; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C064655:V(D)J recombination activating protein 2; D008748:Methylcholanthrene; D007371:Interferon-gamma