细胞因子与PD-L1的联合作用在肿瘤中的研究进展
Research Progress on the Combination of Cytokines and PD-L1 in Tumors
DOI: 10.12677/acm.2025.151215, PDF,   
作者: 鲁容钶, 贾东瑜：内蒙古医科大学第一临床医学院，内蒙古 呼和浩特；郑 健*：内蒙古自治区妇产疾病临床医学研究中心，内蒙古 呼和浩特
关键词: 细胞因子；PD-L1；肿瘤；免疫治疗；Cytokines； PD-L1； Tumor； Immunotherapy
摘要: 抗程序性死亡配体1 (PD-L1)作为经典的免疫检查点分子，与程序性死亡受体1 (PD-1)结合后能够抑制T细胞的活化及多种功能，从而帮助肿瘤细胞逃避免疫系统的攻击。细胞因子是一类调节细胞生长、分化和死亡的蛋白质，可使得T细胞发生功能障碍甚至衰竭，在调控免疫应答过程中发挥重要作用。近年来不断有研究表明，细胞因子与PD-L1在肿瘤中具有复杂的调节关系，其通过PI3K/AKT、JAK/STAT、MAPK等信号通路影响免疫细胞的功能和免疫应答的调节，协同细胞因子与免疫抑制剂在肿瘤治疗临床试验中显示出一定成效。本文旨在探索利用细胞因子与PD-L1相互作用来提高肿瘤免疫治疗的有效性，为日后细胞因子与免疫抑制剂的联合应用在肿瘤中的治疗提供理论研究基础。
Abstract: Anti-procedural death ligand 1 (PD-L1), as a classic immune checkpoint molecule, can inhibit the activation and multiple functions of T cells when combined with programmed death receptor 1 (PD-1), thus helping tumor cells escape the attack of the immune system. Cytokines are a class of proteins that regulate cell growth, differentiation and death, which can cause dysfunction or even failure of T cells and play an important role in regulating immune response. In recent years, continuous studies have shown that cytokines and PD-L1 have a complex regulatory relationship in tumors, which affects the function of immune cells and the regulation of immune responses through PI3K/AKT, JAK/STAT, MAPK and other signaling pathways. Synergistic cytokines and immunosuppressants have shown certain results in tumor treatment clinical trials. This article aims to explore the interaction between cytokines and PD-L1 to improve the effectiveness of tumor immunotherapy, and provide a theoretical research basis for the future combination of cytokines and immunosuppressants in the treatment of tumors.
文章引用：鲁容钶, 贾东瑜, 郑健. 细胞因子与PD-L1的联合作用在肿瘤中的研究进展[J]. 临床医学进展, 2025, 15(1): 1605-1612. https://doi.org/10.12677/acm.2025.151215

参考文献

[1] Ai, L., Xu, A. and Xu, J. (2020) Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond. In: Xu, J., Ed., Regulation of Cancer Immune Checkpoints, Springer, 33-59. [Google Scholar] [CrossRef] [PubMed]
[2] Ghahremanloo, A., Soltani, A., Modaresi, S.M.S. and Hashemy, S.I. (2019) Recent Advances in the Clinical Development of Immune Checkpoint Blockade Therapy. Cellular Oncology, 42, 609-626. [Google Scholar] [CrossRef] [PubMed]
[3] Azimi, M., Manavi, M.S., Afshinpour, M., et al. (2024) Emerging Immunologic Approaches as Cancer Anti-Angiogenic Therapies. Clinical & Translational Oncology.
[4] Qiu, Y., Su, M., Liu, L., Tang, Y., Pan, Y. and Sun, J. (2021) Clinical Application of Cytokines in Cancer Immunotherapy. Drug Design, Development and Therapy, 15, 2269-2287. [Google Scholar] [CrossRef] [PubMed]
[5] Dong, L., Chen, C., Zhang, Y., Guo, P., Wang, Z., Li, J., et al. (2021) The Loss of RNA N6-Adenosine Methyltransferase Mettl14 in Tumor-Associated Macrophages Promotes CD8+ T Cell Dysfunction and Tumor Growth. Cancer Cell, 39, 945-957.e10. [Google Scholar] [CrossRef] [PubMed]
[6] 吴增波, 秘双燕, 晏燕. TNF-α在口腔鳞癌组织中的表达及临床意义[J]. 贵州医科大学学报, 2020, 45(9): 1047-1050, 1066.
[7] 李德辉, 苏伊璠. PD-1/PD-L1与PI3K/AKT交叉对话与乳腺癌变免疫微环境[J]. 中国老年学杂志, 2022, 42(1): 215-218.
[8] 吴潇. 幽门螺旋杆菌诱导的IL-8通过PI3K/AKT信号通路上调PD-L1的表达进而促进胃癌的免疫逃逸[D]: [硕士学位论文]. 合肥: 安徽医科大学, 2021.
[9] 谢晓丽, 邱雨, 王丽娟. 干扰素-γ通过PI3K/Akt/mTOR通路上调程序性死亡受体-配体1促进非霍奇金淋巴瘤细胞增殖[J]. 山东大学学报(医学版), 2023, 61(5): 11-19.
[10] Zhao, R., Song, Y., Wang, Y., Huang, Y., Li, Z., Cui, Y., et al. (2019) PD‐1/PD‐L1 Blockade Rescue Exhausted CD8+ T Cells in Gastrointestinal Stromal Tumours via the PI3K/Akt/mTOR Signalling Pathway. Cell Proliferation, 52, e12571. [Google Scholar] [CrossRef] [PubMed]
[11] Villarino, A.V., Kanno, Y. and O’Shea, J.J. (2017) Mechanisms and Consequences of Jak-STAT Signaling in the Immune System. Nature Immunology, 18, 374-384. [Google Scholar] [CrossRef] [PubMed]
[12] Villarino, A.V., Gadina, M., O’Shea, J.J. and Kanno, Y. (2020) SnapShot: Jak-STAT Signaling II. Cell, 181, 1696-1696.e1. [Google Scholar] [CrossRef] [PubMed]
[13] Salmaninejad, A., Valilou, S.F., Soltani, A., Ahmadi, S., Abarghan, Y.J., Rosengren, R.J., et al. (2019) Tumor-Associated Macrophages: Role in Cancer Development and Therapeutic Implications. Cellular Oncology, 42, 591-608. [Google Scholar] [CrossRef] [PubMed]
[14] 韩垠超. IL-4经STAT6通路对胃癌细胞增殖、侵袭和迁移的影响及机制研究[D]: [硕士学位论文]. 锦州: 锦州医科大学, 2021.
[15] Pucci, M., Raimondo, S., Urzì, O., Moschetti, M., Di Bella, M.A., Conigliaro, A., et al. (2021) Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways. International Journal of Molecular Sciences, 22, Article 12118. [Google Scholar] [CrossRef] [PubMed]
[16] Chan, L., Li, C., Xia, W., Hsu, J., Lee, H., Cha, J., et al. (2019) IL-6/JAK1 Pathway Drives PD-L1 Y112 Phosphorylation to Promote Cancer Immune Evasion. Journal of Clinical Investigation, 129, 3324-3338. [Google Scholar] [CrossRef] [PubMed]
[17] Chen, S., Wang, M., Lu, T., Liu, Y., Hong, W., He, X., et al. (2023) JMJD6 in Tumor-Associated Macrophage Regulates Macrophage Polarization and Cancer Progression via STAT3/IL-10 Axis. Oncogene, 42, 2737-2750. [Google Scholar] [CrossRef] [PubMed]
[18] Schmetterer, K.G. and Pickl, W.F. (2017) The IL-10/STAT3 Axis: Contributions to Immune Tolerance by Thymus and Peripherally Derived Regulatory T‐Cells. European Journal of Immunology, 47, 1256-1265. [Google Scholar] [CrossRef] [PubMed]
[19] Zhang, X., Zeng, Y., Qu, Q., Zhu, J., Liu, Z., Ning, W., et al. (2017) PD-L1 Induced by IFN-γ from Tumor-Associated Macrophages via the JAK/STAT3 and PI3K/AKT Signaling Pathways Promoted Progression of Lung Cancer. International Journal of Clinical Oncology, 22, 1026-1033. [Google Scholar] [CrossRef] [PubMed]
[20] 陈卓. IFN-γ联合TNF-α协同上调PD-L1表达增强hUC-MSCs免疫抑制功能的分子机制研究[D]: [博士学位论文]. 重庆: 中国人民解放军陆军军医大学, 2023.
[21] Wang, Y., Liu, S., Yang, Z., Algazi, A.P., Lomeli, S.H., Wang, Y., et al. (2021) Anti-Pd-1/l1 Lead-In before MAPK Inhibitor Combination Maximizes Antitumor Immunity and Efficacy. Cancer Cell, 39, 1375-1387.e6. [Google Scholar] [CrossRef] [PubMed]
[22] Stutvoet, T.S., Kol, A., de Vries, E.G., de Bruyn, M., Fehrmann, R.S., Terwisscha van Scheltinga, A.G., et al. (2019) MAPK Pathway Activity Plays a Key Role in PD‐L1 Expression of Lung Adenocarcinoma Cells. The Journal of Pathology, 249, 52-64. [Google Scholar] [CrossRef] [PubMed]
[23] Diab, A., Tannir, N.M., Bentebibel, S., Hwu, P., Papadimitrakopoulou, V., Haymaker, C., et al. (2020) Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02). Cancer Discovery, 10, 1158-1173. [Google Scholar] [CrossRef] [PubMed]
[24] Zhang, G., Jiao, Q., Shen, C., Song, H., Zhang, H., Qiu, Z., et al. (2021) Interleukin 6 Regulates the Expression of Programmed Cell Death Ligand 1 in Thyroid Cancer. Cancer Science, 112, 997-1010. [Google Scholar] [CrossRef] [PubMed]
[25] Herzog, T.J., Hays, J.L., Barlin, J.N., Buscema, J., Cloven, N.G., Kong, L.R., et al. (2023) ARTISTRY-7: Phase III Trial of Nemvaleukin Alfa plus Pembrolizumab vs Chemotherapy for Platinum-Resistant Ovarian Cancer. Future Oncology, 19, 1577-1591. [Google Scholar] [CrossRef] [PubMed]
[26] Huseni, M.A., Wang, L., Klementowicz, J.E., Yuen, K., Breart, B., Orr, C., et al. (2023) CD8+ T Cell-Intrinsic IL-6 Signaling Promotes Resistance to Anti-PD-L1 Immunotherapy. Cell Reports Medicine, 4, Article ID: 100878. [Google Scholar] [CrossRef] [PubMed]
[27] Myers, J.A. and Miller, J.S. (2020) Exploring the NK Cell Platform for Cancer Immunotherapy. Nature Reviews Clinical Oncology, 18, 85-100. [Google Scholar] [CrossRef] [PubMed]

为你推荐