title: Strain-specific variation in murine natural killer gene complex contributes to differences in immunosurveillance for urethane-induced lung cancer.
abstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide and results from a complex interaction between carcinogen exposure and inherent susceptibility. Despite its prevalence, genetic factors that predispose to the development of lung cancer remain elusive. Inbred mouse models offer a unique and clinically relevant tool to study genetic factors that contribute to lung carcinogenesis due to the development of tumors that resemble human adenocarcinoma and broad strain-specific variation in cancer incidence after carcinogen administration. Here, we set out to investigate whether strain-specific variability in tumor immunosurveillance contributes to differences in lung cancer. Using bone marrow transplantation, we determined that hematopoietic cells from lung cancer-resistant mice could significantly impede the development of cancer in a susceptible strain. Furthermore, we show that this is not due to differences in tumor-promoting inflammatory changes or variability in immunosurveillance by the adaptive immune system but results from strain-specific differences in natural killer (NK) cell cytotoxicity. Using a newly discovered congenic strain of mice, we show a previously unrecognized role for strain-specific polymorphisms in the natural killer gene complex (NKC) in immunosurveillance for carcinogen-induced lung cancer. Because polymorphisms in the NKC are highly prevalent in man, our data may explain why certain individuals without obvious risk factors develop lung cancer whereas others remain resistant to the disease despite heavy environmental carcinogen exposure.
authors: Departments of Surgery, Pathology and Immunology, and Internal Medicine,The Alvin Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Daniel
authors: D
authors: Kreisel
authors: Andrew E
authors: AE
authors: Gelman
authors: Ryuji
authors: R
authors: Higashikubo
authors: Xue
authors: X
authors: Lin
authors: Haris G
authors: HG
authors: Vikis
authors: J Michael
authors: JM
authors: White
authors: Kelsey A
authors: KA
authors: Toth
authors: Charuhas
authors: C
authors: Deshpande
authors: Beatriz M
authors: BM
authors: Carreno
authors: Ming
authors: M
authors: You
authors: Samantha M
authors: SM
authors: Taffner
authors: Wayne M
authors: WM
authors: Yokoyama
authors: Jack D
authors: JD
authors: Bui
authors: Robert D
authors: RD
authors: Schreiber
authors: Alexander S
authors: AS
authors: Krupnick
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002273:Carcinogens; D002289:Carcinoma, Non-Small-Cell Lung / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D045744:Cell Line, Tumor; D002875:Chromosomes; D006801:Humans; D007113:Immunity, Innate; D007157:Immunologic Surveillance; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011110:Polymorphism, Genetic; D013045:Species Specificity; D014520:Urethane
chemical_list: D002273:Carcinogens; D014520:Urethane