Strain-specific variation in murine natural killer gene complex contributes to differences in immunosurveillance for urethane-induced lung cancer.
Strain-specific variation in murine natural killer gene complex contributes to differences in immunosurveillance for urethane-induced lung cancer.
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DOI：
10.1158/0008-5472.can-12-0908
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发表时间：
2012-09-01
期刊：
影响因子：
11.2
通讯作者：
Krupnick AS
中科院分区：
文献类型：
--
作者：
Kreisel D;Gelman AE;Higashikubo R;Lin X;Vikis HG;White JM;Toth KA;Deshpande C;Carreno BM;You M;Taffner SM;Yokoyama WM;Bui JD;Schreiber RD;Krupnick AS
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 cell (NK) cytotoxicity. Using a newly discovered congenic strain of mice we demonstrate a previously unrecognized role for strain-specific polymorphisms in the natural killer gene complex (NKC) in immunosurveillance for carcinogen-induced lung cancer. Since polymorphisms in the NKC are highly prevalent in man, our data may explain why certain individuals without obvious risk factors develop lung cancer while others remain resistant to the disease despite heavy environmental carcinogen exposure.
