International Journal of Molecular Medical Science, 2025, Vol.15, No.5, 224-234 http://medscipublisher.com/index.php/ijmms 2 26 by the release of damage-associated molecular patterns (DAMPs), such as ATP, calreticulin and HMGB1. These molecules can signal the immune system, help dendritic cells mature, and also activate tumor-specific T-cell responses. In the treatment of non-small cell lung cancer, drugs such as docetaxel and platinum-based combination therapy have been found to have a strong ability to induce ICD. Therefore, in preclinical models, they can enhance the phagocytic ability of tumor cells and also strengthen the anti-tumor immune effect (Gu et al., 2023). Chemotherapy-induced ICD can not only directly kill tumor cells, but also turn the dying cancer cells into the source of tumor antigens, playing a role similar to that of in situ vaccines (Ahmed and Tait, 2020). This process is crucial for activating innate and adaptive immune responses and also lays the foundation for the synergistic effect of the combined use of immunotherapy and chemotherapy. However, not all chemotherapy drugs have the same effect in inducing ICD, which indicates that it is important to choose the appropriate regimen to combine with the therapy (Flieswasser et al., 2020). 3.2 The regulatory effect of chemotherapy on the tumor immune microenvironment Chemotherapy can adjust the composition and function of tumor immune cell populations and has a significant regulatory impact on the tumor immune microenvironment (TME). Studies have shown that neoadjuvant chemotherapy enables more cytotoxic CD8+T cells, tissue-resident memory T cells and B cells to enter the TME of non-small cell lung cancer, thereby enhancing anti-tumor immunity. In addition, chemotherapy can also change the distribution location and quantity of regulatory T cells (TreGs). The more Tregs infiltrate and the closer they are to CD8+ T cells, the better the patient's response to chemotherapy will be, and the longer the recurrences survival time will be (Cai et al., 2024). In addition to allowing more active immune cells to enter, chemotherapy can also reduce immunosuppressive components in the tumor microenvironment (TME), such as tumor-associated macrophages and cancer-associated fibroblasts, while promoting the activation of antigen-presenting cells. The combined effect of these changes can transform the TME from the "cold" state of immunosuppression to the "hot" state that is more likely to stimulate the immune response, thereby enhancing the effect of subsequent or concurrent immunotherapy (Kang et al., 2021). 3.3 The synergistic anti-tumor effect of immunotherapy and chemotherapy When chemotherapy and immunotherapy are used together, they will utilize complementary mechanisms to achieve a synergistic effect in combating tumors. Chemical-induced ICD enables more tumor antigens to be released and presented, while immunotherapy (especially PD-1/PD-L1 blockade therapy) removes inhibitory signals on T cells, making the immune response stronger and more durable (Zhou et al., 2023; Wang, 2025). Both preclinical and clinical studies have shown that compared with the use of one of these treatments alone, this synergistic effect can increase patient survival rates, delay tumor growth, and enable more active immune cells to enter the tumor (Flieswasser et al., 2023). The key lies in the timing and sequence of chemotherapy and immunotherapy, which will affect the intensity of their synergistic effect. Research has found that chemotherapy followed by immunotherapy (sequential administration) can further increase the survival rate of non-small cell lung cancer models and enhance the activity of the immune system. These results demonstrate the rationality of the combined use of chemotherapy and immunotherapy, and also support the continuous improvement of treatment regimens to achieve better clinical outcomes (Flieswasser et al., 2020; Kang et al., 2021). 4 Meta-Analysis 4.1 Literature search strategy and inclusion criteria of studies The recent meta-analysis adopted a comprehensive and systematic search approach to evaluate the survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy for non-small cell lung cancer. Researchers searched major databases such as PubMed, Embase, Web of Science and Cochrane Library, and also supplemented meeting minutes and clinical trial registration information. Screen those randomized controlled
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