College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
Biomed Pharmacother. 2023 Oct;166:115336. doi: 10.1016/j.biopha.2023.115336. Epub 2023 Aug 15.
Lung cancer (LC) is one of the leading causes of cancer-related deaths worldwide, with a significant morbidity and mortality rate, endangering human life and health. The introduction of immunotherapies has significantly altered existing cancer treatment strategies and is expected to improve immune responses, objective response rates, and survival rates. However, a better understanding of the complex immunological networks of LC is required to improve immunotherapy efficacy further. Tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs) are significantly expressed by LC cells, which activate dendritic cells, initiate antigen presentation, and activate lymphocytes to exert antitumor activity. However, as tumor cells combat the immune system, an immunosuppressive microenvironment forms, enabling the enactment of a series of immunological escape mechanisms, including the recruitment of immunosuppressive cells and induction of T cell exhaustion to decrease the antitumor immune response. In addition to the direct effect of LC cells on immune cell function, the secreting various cytokines, chemokines, and exosomes, changes in the intratumoral microbiome and the function of cancer-associated fibroblasts and endothelial cells contribute to LC cell immune escape. Accordingly, combining various immunotherapies with other therapies can elicit synergistic effects based on the complex immune network, improving immunotherapy efficacy through multi-target action on the tumor microenvironment (TME). Hence, this review provides guidance for understanding the complex immune network in the TME and designing novel and effective immunotherapy strategies for LC.
肺癌（LC）是全球癌症相关死亡的主要原因之一，具有较高的发病率和死亡率，危及人类生命和健康。免疫疗法的引入显著改变了现有的癌症治疗策略，有望改善免疫反应、客观缓解率和生存率。然而，需要更好地了解 LC 的复杂免疫网络，以进一步提高免疫疗法的疗效。肿瘤相关抗原（TAA）和肿瘤特异性抗原（TSA）在 LC 细胞中高度表达，它们激活树突状细胞，启动抗原呈递，并激活淋巴细胞发挥抗肿瘤活性。然而，随着肿瘤细胞与免疫系统的对抗，形成了免疫抑制微环境，从而使一系列免疫逃逸机制得以实施，包括招募免疫抑制细胞和诱导 T 细胞耗竭，从而降低抗肿瘤免疫反应。除了 LC 细胞对免疫细胞功能的直接影响外，各种细胞因子、趋化因子和外泌体的分泌、肿瘤内微生物组的变化以及癌相关成纤维细胞和内皮细胞的功能改变都有助于 LC 细胞的免疫逃逸。因此，将各种免疫疗法与其他疗法相结合，可以根据复杂的免疫网络产生协同效应，通过对肿瘤微环境（TME）的多靶点作用提高免疫疗法的疗效。因此，本综述为理解 TME 中的复杂免疫网络以及设计针对 LC 的新型有效免疫治疗策略提供了指导。
