Mechanisms of Immunosurveillance for Lung Cancer

肺癌仍然是西方世界与癌症相关的主要死亡原因 正在加紧努力，以发展辅助疗法，以治疗 治疗这种疾病的方法。而针对获得性免疫的免疫治疗 T淋巴细胞形式的反应在几个实体肿瘤中取得了成功， 如黑色素瘤和前列腺癌，在肺癌方面一直非常不成功 癌症。我们最近发现，与其他实体肿瘤不同，与生俱来的 获得性免疫系统在肺免疫监测中的关键作用 癌症。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。在本提案中，我们重点介绍了 自然杀伤细胞在肺癌免疫监测和免疫治疗中的应用。我们计划 小鼠肺癌免疫监视机制的研究 并将评估人类对这种疾病易感的免疫学基础。在 首先，我们将研究激活受体NKp46在肺癌特异性中的作用 激活NK细胞。在第二个目标中，我们将评估NK使用的机制 在体内控制肺癌的细胞和第三个目标，我们将重点放在抑制 受体Ly49C与不同菌株NK细胞抗癌活性的差异 细胞。在第四个也是最终目标中，我们计划评估人类NK的许可状态 细胞和肺癌的易感性。 1

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