Journal of Vaccine Research, 2025, Vol.15, No.1, 45-55 http://medscipublisher.com/index.php/jvr 46 inhalable vaccines and preventive vaccines. It is expected to provide useful references for the application of immunotherapy for non-small cell lung cancer in clinical practice and research priorities in the future. 2 The Immunological Landscape of Non-Small Cell Lung Cancer 2.1 Composition and functional disorders of immune cells in the tumor microenvironment The tumor-surrounding environment (TME) of non-small cell lung cancer (NSCLC) is like a complex "cell network", which contains immune cells and stromal cells, including CD8+T cells that can kill tumors, CD4+T cells that assist, and Tregs cells that play a regulatory role. There are also tumor-associated macrophages, myeloid-derived suppressor cells (MDSCs), dendritic cells and natural killer cells. In patients with non-small cell lung cancer, the balance between immune-activating cells and immune-suppressing cells is often disrupted. The number of Tregs, MDSCs, and a type of macrophage called M2-polarized macrophages increases, weakening the body's ability to fight tumors and instead helping tumors grow larger (Santaniello et al., 2019; Conforti et al., 2021; Jin and Zhao, 2022). Cytokines, chemokines and metabolic factors also affect the tumor-surrounding environment. They either help immune cells approach the tumor or enhance immunosuppression, keeping the tumor-surrounding environment constantly changing (Kim and Cho, 2022; Yu et al., 2025). The immune cells in the surrounding environment of non-small cell lung cancer tumors "do not work well", which is a manifestation of the tumor evading immune attack. Lymphocytes (TILs) in tumors, especially CD8+T cells, often "go on strike", manifested as an increase in immunosuppressor receptors and a decline in their ability to attack tumors (Conforti et al., 2021). Metabolic problems such as hypoxia and insufficient nutrition in tumors can weaken the combat effectiveness of immune cells, but allow the cells that play an inhibitory role to survive (Yu et al., 2025). Moreover, recent studies have found that cancer cells can "shove" problematic mitochondria into TILs cells, causing metabolic problems and premature "aging" in them. As a result, the body's ability to fight tumors becomes weaker, and the effect of vaccination treatment also deteriorates (Ikeda et al., 2025). These abnormal immune conditions not only weaken the body's innate ability to fight tumors, but also limit the effectiveness of immunotherapy, including therapeutic vaccines. 2.2 Tumor antigen types associated with NSCLC Tumor-associated antigens (TAAs) and tumor-specific antigens (tsa, also known as neoantigens) are key to the development of therapeutic vaccines for non-small cell lung cancer. TAAs are human autoproteins such as MAGE-A3 and WT1 that are excessive in quantity or abnormally expressed in tumor cells. Although their use may cause immune tolerance or autoimmune problems in the human body, the immune system can recognize them. In contrast, tsa is produced by gene mutations specific to tumor cells and is particularly prone to triggering immune responses, making it an ideal target for customizing personalized vaccines (Anichini et al., 2020; Conforti et al., 2021). Identifying and confirming these antigens is of great significance for the development of effective vaccines that can generate strong and precise immune responses in the human body. The situation of non-small cell lung cancer varies from person to person, which leads to significant differences in the types of TAAs and tsa in different patients. Even in different parts of the same tumor, these antigens are not the same (Conforti et al., 2021). Patients with non-small cell lung cancer often have situations such as non-expression of antigens, defective processing, or neoantigen "silencing", which enables tumors to evade immune attack and also makes immunotherapy ineffective (Anichini et al., 2020). Understanding the diversity and expression forms of these antigens is crucial for the development of effective therapeutic vaccines, as only in this way can the best "target of attack" be selected to overcome the individual differences in tumors and enable the human body to generate lasting anti-tumor immunity. 2.3 Immune evasion mechanisms and their impact on vaccine efficacy There are many ways for non-small cell lung cancer to evade immune attacks and render therapeutic vaccines ineffective. These methods include: Due to the absence of HLA molecules, tumors cannot normally "display" antigens; The number of immune checkpoint molecules like PD-L1 has increased; Secrete cytokines that suppress immunity; Recruit Tregs and MDSCs, which suppress the immune system (Santaniello et al., 2019; Anichini et al., 2020; Hong et al., 2020; Jin and Zhao, 2022; Kim and Cho, 2022). Tumor cells can also make T cells "powerless
RkJQdWJsaXNoZXIy MjQ4ODYzNA==