The Phenotype and function of Natural Killer Cells in KRAS-induced Lung Cancer
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- 英文论文题名：The Phenotype and function of Natural Killer Cells in KRASinduced Lung Cancer
- 论文作者：Cong Jingjing ; Sun Rui ; Tian Zhigang ; Wei Haiming
- 英文论文作者：Cong Jingjing ; Sun Rui ; Tian Zhigang ; Wei Haiming ; Institute of Immunology ; School of Life Sciences ; University of Science and Technology of China
- 年：2016
- 作者机构：Institute of Immunology,School of Life Sciences,University of Science and Technology of China;
- 英文论文关键词：NK cells ; Lung cancer ; Tumor environment
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会壁报交流集
- 英文会议录名称：Proceedings of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R734.2
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：2
- 文件大小：413k
- 原文格式：D
- 会议级别：全国
摘要
Lung cancer is the leading cause of cancer incidence in the world,resulting in the largest number of cancer-related deaths.Activating mutations of the Kras oncogene are found in 25% to 50% of human lung adenocarcinomas,whichare the most frequent alterations in lung adenocarcinomas,and Kras is still considered as an undruggable target.NK cell is a member of natural immunity,playing important roles in host defense,especially in clearing microbes and anti-tumor.In the lung of mice,NK cells make up the highest percentage(10%) of lymphocytes compared with other tissues,and the total number of NK cells is second only to spleen NK cells.We use LSL-Kras G12 D mice model to achieve spontaneous lung cancer by use of Lenti-Cre infection,so we can research NK cells in the different stages of lung cancer.We sorted normal lung NK cells and tumor infiltrating NK cells(TINK),and found that many tumor-promoting genes including Ctsk,Mmp12,Mmp13,Gpnmb were upregulated gradually in the TINK with the aggravation of tumor by gene chip analysis and real time PCR analysis.We used IHC and IF to localize NK cells and characterized the phenotype of NK cells in the lung,spleen and blood of WT mice and Kras G12 D mice.TINK displayed distinctive alterations:IFNγ,TNFα,CD107 a,CD27 and Ki67 were downregulated,meanwhile GPNMB was upregulated,implying TINK were less functional and even may promote tumor progress.We detected the cytotoxicity of normal lung NK and TINK,and the cytotoxicity of TINK was weaker obviously as expected.These results suggest that tumor environment influence NK cells,and remolded NK cells may promote tumor progress in turn.We will focus on the relation of tumor environment and NK cells in future.
Lung cancer is the leading cause of cancer incidence in the world,resulting in the largest number of cancer-related deaths.Activating mutations of the Kras oncogene are found in 25% to 50% of human lung adenocarcinomas,whichare the most frequent alterations in lung adenocarcinomas,and Kras is still considered as an undruggable target.NK cell is a member of natural immunity,playing important roles in host defense,especially in clearing microbes and anti-tumor.In the lung of mice,NK cells make up the highest percentage(10%) of lymphocytes compared with other tissues,and the total number of NK cells is second only to spleen NK cells.We use LSL-Kras G12 D mice model to achieve spontaneous lung cancer by use of Lenti-Cre infection,so we can research NK cells in the different stages of lung cancer.We sorted normal lung NK cells and tumor infiltrating NK cells(TINK),and found that many tumor-promoting genes including Ctsk,Mmp12,Mmp13,Gpnmb were upregulated gradually in the TINK with the aggravation of tumor by gene chip analysis and real time PCR analysis.We used IHC and IF to localize NK cells and characterized the phenotype of NK cells in the lung,spleen and blood of WT mice and Kras G12 D mice.TINK displayed distinctive alterations:IFNγ,TNFα,CD107 a,CD27 and Ki67 were downregulated,meanwhile GPNMB was upregulated,implying TINK were less functional and even may promote tumor progress.We detected the cytotoxicity of normal lung NK and TINK,and the cytotoxicity of TINK was weaker obviously as expected.These results suggest that tumor environment influence NK cells,and remolded NK cells may promote tumor progress in turn.We will focus on the relation of tumor environment and NK cells in future.
Lung cancer is the leading cause of cancer incidence in the world,resulting in the largest number of cancer-related deaths.Activating mutations of the Kras oncogene are found in 25% to 50% of human lung adenocarcinomas,whichare the most frequent alterations in lung adenocarcinomas,and Kras is still considered as an undruggable target.NK cell is a member of natural immunity,playing important roles in host defense,especially in clearing microbes and anti-tumor.In the lung of mice,NK cells make up the highest percentage(10%) of lymphocytes compared with other tissues,and the total number of NK cells is second only to spleen NK cells.We use LSL-Kras G12 D mice model to achieve spontaneous lung cancer by use of Lenti-Cre infection,so we can research NK cells in the different stages of lung cancer.We sorted normal lung NK cells and tumor infiltrating NK cells(TINK),and found that many tumor-promoting genes including Ctsk,Mmp12,Mmp13,Gpnmb were upregulated gradually in the TINK with the aggravation of tumor by gene chip analysis and real time PCR analysis.We used IHC and IF to localize NK cells and characterized the phenotype of NK cells in the lung,spleen and blood of WT mice and Kras G12 D mice.TINK displayed distinctive alterations:IFNγ,TNFα,CD107 a,CD27 and Ki67 were downregulated,meanwhile GPNMB was upregulated,implying TINK were less functional and even may promote tumor progress.We detected the cytotoxicity of normal lung NK and TINK,and the cytotoxicity of TINK was weaker obviously as expected.These results suggest that tumor environment influence NK cells,and remolded NK cells may promote tumor progress in turn.We will focus on the relation of tumor environment and NK cells in future.
引文