Yagui-Beltrán Adam, Coussens Lisa M, Jablons David M
Post-doctoral Fellow, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco.
US Oncol. 2009;58(1):40-48. doi: 10.17925/ohr.2009.05.1.40.
Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these insights and advances in surgery and chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains poor. Nonetheless, significant effort is being focused on advancing translational research evaluating the efficacy of novel targeted therapeutic strategies for lung cancer. Illustrative examples of this include antagonists of the epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds targeting growth factors and/or their receptors that regulate tumor-associated angiogenic programs. In addition, with the increased awareness of the significant role chronically activated leukocytes play as potentiators of solid-tumor development, the role of innate and adaptive immune cells as regulators of lung carcinogenesis is being examined. While some of these studies are examining how novel therapeutic strategies may enhance the efficacy of lung cancer vaccines, others are evaluating the intrinsic characteristics of the immune response to lung cancer in order to identify rate-limiting molecular and/or cellular programs to target with novel anticancer therapeutics. In this article, we explore important aspects of the immune system and its role in regulating normal respiratory homeostasis compared with the immune response accompanying development of lung cancer. These hallmarks are then discussed in the context of recent efforts to develop lung cancer vaccines, where we have highlighted important concepts that must be taken into consideration for future development of novel therapeutic strategies and clinical trials assessing their efficacy.
肺癌是美国所有癌症死亡的主要原因。国际科学和临床界在理解肺癌发生的特定分子机制方面取得了重大进展；然而，尽管有这些见解以及手术和放化疗方面的进步，非小细胞肺癌（NSCLC）的预后仍然很差。尽管如此，大量努力正集中在推进转化研究，以评估新型肺癌靶向治疗策略的疗效。这方面的示例包括表皮生长因子受体（EGFR）拮抗剂、吉非替尼和厄洛替尼等酪氨酸激酶抑制剂（TKIs），以及针对调节肿瘤相关血管生成程序的生长因子和/或其受体的各种抗血管生成化合物。此外，随着人们越来越意识到慢性激活的白细胞作为实体瘤发展增强剂所起的重要作用，先天免疫细胞和适应性免疫细胞作为肺癌发生调节因子的作用正在得到研究。虽然其中一些研究在探讨新型治疗策略如何提高肺癌疫苗的疗效，但其他研究则在评估对肺癌免疫反应的内在特征，以便确定可用新型抗癌疗法靶向的限速分子和/或细胞程序。在本文中，我们探讨了免疫系统的重要方面及其在调节正常呼吸稳态中的作用，并与肺癌发生时伴随的免疫反应进行了比较。然后在最近开发肺癌疫苗的努力背景下讨论了这些特征，我们强调了未来开发新型治疗策略和评估其疗效的临床试验时必须考虑的重要概念。
