Mechanisms of Immunosurveillance for Lung Cancer

肺癌的免疫监视机制

• 批准号: 8629870
• 负责人: ALEXANDER S. KRUPNICK
• 金额: --
• 依托单位: ST. LOUIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8629870
• 关键词: Adjuvant Therapy; Adoptive Transfer; Adult; Animal Model; Animals; Applications Grants; Atypical lymphocyte; Cause of Death; Cells; Chromosomes, Human, Pair 19; Chromosomes, Human, Pair 6; Clinical Trials; Defect; Development; Disease; Disease Resistance; Etiology; Genetic Polymorphism; Goals; Growth; Growth and Development function; Histocompatibility Antigens Class I; Human; Immune; Immune System Diseases; Immune response; Immune system; Immunoglobulins; Immunologic Monitoring; Immunologics; Immunotherapy; In Vitro; Individual; Individual Differences; Inherited; Killer Cells; Licensing; Ligands; Ligation; MHC Class I Genes; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Mediating; Methods; Mouse Strains; Mus; Mutate; NK Cell Activation; Natural Killer Cells; Non-Small-Cell Lung Carcinoma; Play; Population; Predisposition; Process; Prostate; Proteins; Protocols documentation; Recording of previous events; Resistance; Role; Shapes; Smoking; Solid Neoplasm; T-Lymphocyte; Technology; Testing; Tumor Angiogenesis; Tumor Antigens; Vaccination; Variant; Western World; Zinc Fingers; arm; base; cancer immunotherapy; cytotoxic; cytotoxicity; endonuclease; fibrosarcoma; immunogenicity; improved; in vivo; kidney cell; man; melanoma; mouse model; pre-clinical; public health relevance; receptor; translational clinical trial; tumor

Lung cancer remains the major cancer-related cause of death in the Western World and intense efforts are directed toward the development of adjuvant therapy for the treatment of this disease. While immunotherapy targeting the adaptive immune response in the form of T lymphocytes has been successful for several solid tumors, such as melanoma and prostate cancer, it has been extremely unsuccessful in lung cancer. We have recently discovered that, unlike other solid tumors, the innate rather than adaptive immune system plays a critical role in immunosurveillance for lung cancer. Furthermore, individual differences in natural killer cells (NK cells) play a role in susceptibility or resistance to this disease. In this proposal we focus on the role of natural killer cells in immunosurveillance and immunotherapy of lung cancer. We plan to explore mechanistic aspects of lung cancer immunosurveillance in a mouse model and will evaluate the immunologic basis of human susceptibility to this disease. In the first aim we will study the role of the activating receptor NKp46 in lung cancer-specific activation of NK cells. In the second aim we will evaluate the mechanisms used by NK cells to control lung cancer in vivo and in the third aim we will focus on the inhibitory receptor Ly49C as it relates to strain-specific differences in anti-cancer activity of NK cells. In the fourth and final aim we plan to evaluate the licensing status of human NK cells and susceptibility to lung cancer. 1

肺癌仍然是西方世界主要的癌症相关死亡原因， 目前正致力于开发用于这些疾病的辅助治疗。 治疗这种疾病。而针对适应性免疫的免疫疗法 T淋巴细胞形式的应答已经成功地用于几种实体瘤， 例如黑色素瘤和前列腺癌，但在肺癌中非常不成功， 癌我们最近发现，与其他实体瘤不同， 适应性免疫系统在肺的免疫监视中起着关键作用， 癌此外，自然杀伤细胞（NK细胞）的个体差异在 对这种疾病的易感性或抵抗力。在本建议中，我们重点关注以下方面的作用： 自然杀伤细胞在肺癌免疫监视和免疫治疗中的应用。我们计划 在小鼠模型中探索肺癌免疫监视的机制方面 并将评估人类对这种疾病易感性的免疫学基础。在 第一个目的，我们将研究活化受体NKp46在肺癌特异性 NK细胞的激活。在第二个目标中，我们将评估NK使用的机制 细胞来控制体内肺癌，在第三个目标中，我们将专注于抑制 受体Ly49C，因为它涉及NK细胞抗癌活性的菌株特异性差异 细胞在第四个也是最后一个目标中，我们计划评估人类NK细胞的许可状态。 细胞和肺癌易感性。 1