International Journal of Molecular Medical Science, 2025, Vol.15, No.5, 224-234 http://medscipublisher.com/index.php/ijmms 2 25 the scope and consistency of survival improvement, identify the deficiencies in current research, and explain the clinical and scientific significance of these combined treatment regimens. This is of great value for guiding individualized treatment, improving patient prognosis and providing direction for future NSCLC treatment research. 2 PD-1/PD-L1 Signaling Pathway and its Role in NSCLC 2.1 Molecular mechanisms of tumor immune evasion Tumor cells of non-small cell lung cancer (NSCLC) evade the surveillance of the immune system in multiple ways, among which the PD-1/PD-L1 pathway is one of the main mechanisms. PD-L1 is expressed on tumor cells and tumor-infiltrating immune cells. It can bind to the PD-1 receptor on activated T cells, reduce the activity of T cells, and enable tumor cells to evade the damage caused by the immune system (Majem et al., 2021). This combination not only reduces the response of cytotoxic T cells, but also weakens the function of T cells, thereby helping tumor growth and making it easier for them to evade the immune system (Hong et al., 2020). Recent studies have further clarified the molecular regulatory mode of PD-L1 expression in NSCLC. For instance, studies have shown that the NSUN2/ALYREF axis and the circ-CPA4/let-7 miRNA/PD-L1 axis can increase the expression of PD-L1, help tumors evade the immune system, and also deteriorate the therapeutic effect (Yang et al., 2025). These findings indicate that the process by which non-small cell lung cancer evades the immune system is complex, and also demonstrate the importance of restoring effective anti-tumor immunity by targeting the PD-1/PD-L1 pathway. 2.2 Types and representative drugs of PD-1/PD-L1 inhibitors PD-1/PD-L1 inhibitors are monoclonal antibodies designed to prevent the binding between PD-1 and PD-L1, thereby enabling T cells to regain their role in combating tumors. At present, the most widely used PD-1 inhibitors are nivolumab and pembrolizumab, while atezolizumab and duvazumab are commonly used PD-L1 inhibitors (Majem et al., 2021). These drugs were soon approved for first-line treatment of advanced NSCLC because they can prolong the survival of patients and have relatively good safety (Qu et al., 2021). In addition to these commonly used drugs, new drugs such as Camrelizumab, Sintilimab and Sugemalimab have been put into use or are undergoing clinical research, providing more treatment options. When choosing drugs and combination therapy regimens, PD-L1 expression level, histological type and the patient's own condition are usually referred to, which reflects that the treatment of NSCLC is developing towards personalized medicine (Grant et al., 2021; Fu et al., 2025). 2.3 Limitations of monotherapy and the necessity of optimization Although considerable progress has been made in the monotherapy with PD-1/PD-L1 inhibitors, only a small number of patients with non-small cell lung cancer, especially those with high PD-L1 expression, can obtain significant benefits from it. The proportion of disease remission after treatment is usually between 20% and 40% (Grant et al., 2021). Drug resistance of patients to a single treatment, whether it exists from the very beginning or emerges later, remains a major issue. This is usually due to the complex factors of the tumor itself and microenvironmental factors, which prevent the immune response from being sustained (Zhang et al., 2020). To address these issues, researchers have proposed a variety of combination treatment options, among which the most common one is to use it in conjunction with chemotherapy. This approach can enhance the therapeutic effect and enable more patients to benefit from immunotherapy. Studies show that combined therapy can improve the survival rate of patients, but it may also bring more immune-related side effects. Therefore, it is necessary to carefully select appropriate patients and continue to study how to improve the treatment plan (Qu et al., 2021; Fu et al., 2025). 3 The Biological Mechanism of Combined Chemotherapy 3.1 Chemotherapy-induced immunogenic cell death Chemotherapy can cause a type of tumor cell death called immunogenic cell death (ICD), which is characterized
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