title: Adaptive immunity does not strongly suppress spontaneous tumors in a Sleeping Beauty model of cancer.
abstract: The tumor immunosurveillance hypothesis describes a process by which the immune system recognizes and suppresses the growth of transformed cancer cells. A variety of epidemiological and experimental evidence supports this hypothesis. Nevertheless, there are a number of conflicting reports regarding the degree of immune protection conferred, the immune cell types responsible for protection, and the potential contributions of immunosuppressive therapies to tumor induction. The purpose of this study was to determine whether the adaptive immune system actively suppresses tumorigenesis in a Sleeping Beauty (SB) mouse model of cancer. SB transposon mutagenesis was performed in either a wild-type or immunocompromised (Rag2-null) background. Tumor latency and multiplicity were remarkably similar in both immune cohorts, suggesting that the adaptive immune system is not efficiently suppressing tumor formation in our model. Exceptions included skin tumors, which displayed increased multiplicity in wild-type animals, and leukemias, which developed with shorter latency in immune-deficient mice. Overall tumor distribution was also altered such that tumors affecting the gastrointestinal tract were more frequent and hemangiosarcomas were less frequent in immune-deficient mice compared with wild-type mice. Finally, genetic profiling of transposon-induced mutations identified significant differences in mutation prevalence for a number of genes, including Uba1. Taken together, these results indicate that B and T cells function to shape the genetic profile of tumors in various tumor types, despite being ineffective at clearing SB-induced tumors. To our knowledge, this study represents the first forward genetic screen designed to examine tumor immunosurveillance mechanisms.
authors.affiliation: Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Rogers
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Olivier
authors.forename: David K
authors.initials: DK
authors.lastname: Meyerholz
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Dupuy
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D007938:Leukemia / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D008546:Melanoma, Experimental / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015166:Monitoring, Immunologic; D016296:Mutagenesis; D019895:Transposases / Q000235:genetics / Q000627:therapeutic use*; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology*
chemical_list: D019895:Transposases; C494471:sleeping beauty transposase, human