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Yanglin DENG, Pan LI, Lisha BI, Wenjie LU, Yani MA. Evaluation of the Anti-Tumor Activity of PD-1/PD-L1 Inhibitors Combined with Cisplatin Based on a Jurkat and Lung Cancer Cell Co-Culture Model[J]. Journal of Kunming Medical University.
Citation: Yanglin DENG, Pan LI, Lisha BI, Wenjie LU, Yani MA. Evaluation of the Anti-Tumor Activity of PD-1/PD-L1 Inhibitors Combined with Cisplatin Based on a Jurkat and Lung Cancer Cell Co-Culture Model[J]. Journal of Kunming Medical University.

Evaluation of the Anti-Tumor Activity of PD-1/PD-L1 Inhibitors Combined with Cisplatin Based on a Jurkat and Lung Cancer Cell Co-Culture Model

  • Received Date: 2026-01-16
    Available Online: 2026-06-12
  •   Objective  To establish an in vitro co-culture model of Jurkat cells and lung cancer cells, and to evaluate the in vitro anti-tumor activity of PD-1/PD-L1 inhibitors combined with cisplatin.   Methods  Activated Jurkat cells were co-cultured with HCC95 and A549 cells at different ratios, respectively. The experiment was divided into a cisplatin monotherapy group and combination therapy groups (cisplatin combined with camrelizumab, tislelizumab, or toripalimab). After 24 hours of intervention, cell viability, apoptosis rate, and the expression/secretion levels of PD-1, PD-L1, IL-2, and IFN-γ were detected using CCK-8 assay, flow cytometry, Western blot, and ELISA.   Results  The in vitro co-culture models of Jurkat/A549 (ratio 5∶1) and Jurkat/HCC95 (ratio 3∶1) were successfully established. After drug administration, compared with the cisplatin monotherapy group, the viability and PD-L1 expression of lung cancer cells in the combination therapy groups were significantly decreased (P < 0.05), and the apoptosis rates were significantly increased (P < 0.01). Furthermore, in the camrelizumab and tislelizumab combination groups, the viability of Jurkat cells, as well as the PD-1 expression and IFN-γ secretion levels, were significantly increased (P < 0.05).   Conclusion  PD-1/PD-L1 inhibitors combined with cisplatin exhibit a significant synergistic anti-tumor effect in the in vitro lung cancer model.
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  • [1]
    中华人民共和国国家卫生健康委员会. 原发性肺癌诊疗指南(2022年版)[J]. 中国合理用药探索, 2022, 19(9): 1-28. doi: 10.13455/j.cnki.cjcor.113494-2024-2024-0127
    [2]
    Siegel R L, Miller K D, Fuchs H E, et al. Cancer statistics, 2021[J]. CA: A Cancer Journal for Clinicians, 2021, 71(1): 7-33.
    [3]
    Thai AA, Solomon BJ, Sequist LV, et al. Lung cancer[J]. The Lancet, 2021, 398(10299): 535-554. doi: 10.1016/S0140-6736(21)00312-3
    [4]
    Paz-Ares L, Vicente D, Tafreshi A, et al. A randomized, placebo-controlled trial of pembrolizumab plus chemotherapy in patients with metastatic squamous NSCLC: Final overall survival analysis of KEYNOTE-407[J]. Journal of Thoracic Oncology, 2021, 16(11): 1971-1980.
    [5]
    孙浩, 吴一龙. PD-1/PD-L1抑制剂单药或联合铂类双药化疗对PD-L1高表达的一线非鳞状非小细胞肺癌有效性的真实世界研究[J]. 肿瘤防治研究, 2023, 50(8): 820-829.
    [6]
    Socinski M A, Jotte R M, Cappuzzo F, et al. Association of tissue tumor mutational burden (tTMB) with outcomes with pembrolizumab (pembro) plus chemotherapy (chemo) versus chemo for metastatic nonsquamous NSCLC (nsqNSCLC) in KEYNOTE-021, 189, and 407[J]. Journal of Clinical Oncology, 2022, 40(16): 9019-9019.
    [7]
    Rodriguez-Abreu D, Powell S F, Hochmair M J, et al. Pemetrexed plus platinum with or without pembrolizumab in patients with metastatic nonsquamous NSCLC: 5-year update from KEYNOTE-189[J]. Journal of Thoracic Oncology, 2021, 16(3): S224-S225.
    [8]
    Hellmann M D, Nathanson T, Rizvi H, et al. Genomic features of response to combination immunotherapy in non-small cell lung cancer[J]. Cancer Cell, 2021, 39(7): 1018-1032.
    [9]
    Bejarano L, Jordão MJC, Joyce JA, et al. Therapeutic targeting of the tumor microenvironment[J]. Cancer Discovery, 2021, 11(4): 933-959. doi: 10.1158/2159-8290.CD-20-1808
    [10]
    Zhang W, Li Y, Chen X, et al. Sintilimab reverses T-cell exhaustion and enhances antitumor immunity in 3D co-culture models of pancreatic ductal adenocarcinoma[J]. Journal for ImmunoTherapy of Cancer, 2024, 13(12): 218-224.
    [11]
    Li M, Wang Y, Liu Y, et al. Metabolic reprogramming of myeloid cells by tumor-derived lactate promotes PD-L1-mediated immunosuppression[J]. Cancer Cell., 2023, 41(5): 932-948.
    [12]
    Zhao Y, Lukashev M, Dong Y, et al. PD-1 controls CD8+ T cell metabolic adaptation to the tumor microenvironment[J]. Nature., 2023, 615(7951): 441-448.
    [13]
    Zhang Y, Du X, Liu M, et al. Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy[J]. Cell Research, 2023, 33(1): 89-92. doi: 10.1158/2326-6074.tumimm19-b3
    [14]
    June C H, O'Connor R S, Kawalekar O U, et al. CAR T cell immunotherapy for human cancer[J]. Science, 2021, 371(6536): 1194-1200.
    [15]
    Binnewies M, Mujal A M, Pollack J L, et al. Unleashing type-2 dendritic cells to drive protective antitumor CD4+ T cell immunity[J]. Cell, 2021, 184(22): 5567-5585. doi: 10.1016/j.cell.2019.02.005
    [16]
    Sokolovskaya A, Korneeva E, Zaichenko D, et al. Changes in the Surface Expression of Intercellular Adhesion Molecule 3, the Induction of Apoptosis, and the Inhibition of Cell-Cycle Progression of Human Multidrug-Resistant Jurkat/A4Cells Exposed to a Random Positioning Machine[J]. International Journal of Molecular Sciences, 2020, 21(3): 855-863. doi: 10.3390/ijms21030855
    [17]
    Wang Z, Xu Y, Lu H, et al. CD8+ T cell exhaustion and senescence in cancer immunotherapy[J]. Frontiers in Immunology, 2022, 13: 992-998. doi: 10.1016/j.canlet.2022.216043
    [18]
    Zhang Q, Jia Q, Zhang J, et al. USP15 prevents T lymphocyte senescence and antitumor immunity[J]. Cellular & Molecular Immunology, 2021, 18(7): 1761-1771.
    [19]
    Galletti G, De Simone G, Mazza E M C, et al. Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans[J]. Nature Immunology, 2023, 24(9): 1556-1568. doi: 10.1038/s41590-020-0791-5
    [20]
    唐铭. 抗VEGF-PD-1双特异重组抗体的构建及生物学功能研究[D]. 西南医科大学, 2021.
    [21]
    Poggio M, Hu T, Pai C C, et al. Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory[J]. Cell, 2021, 184(18): 4713-4732.
    [22]
    李国萃. IFN-α2诱导的CD8细胞应答对SIV潜伏/激活态CD4细胞的杀伤作用研究[D]. 中国医学科学院, 2021.
    [23]
    王思渊, 鲁辉. PD-1/PD-L1类单抗药物在肿瘤治疗中的应用进展[J]. 中国生物制品学杂志, 2023, 36(1): 105-118.
    [24]
    Sharma P, Goswami S, Raychaudhuri D, et al. Immune checkpoint therapy-current perspectives and future directions[J]. Cell, 2021, 184(7): 1654-1661.
    [25]
    Chen X, Gao A, Zhang F, et al. ILT4 inhibition prevents TAM- and dysfunctional T cell–mediated immunosuppression and enhances the efficacy of anti–PD-L1 therapy in NSCLC with EGFR activation[J]. Theranostics, 2021, 11(7): 3392-3416. doi: 10.7150/thno.52435
    [26]
    Jiang Y, Chen M, Nie H, et al. PD-1 and PD-L1 in cancer immunotherapy: Clinical implications and future considerations[J]. Molecular Cancer, 2023, 22(1): 106-121.
    [27]
    Liu S, Zhang Z, Li Y, et al. FGFR1 promotes PD-L1 expression via STAT3 activation in non-small cell lung cancer[J]. Journal for ImmunoTherapy of Cancer, 2022, 10(8): 4875-4883.
    [28]
    Zhu P, Jin Z, Kang G, et al. Alpha5 nicotinic acetylcholine receptor mediated immune escape of lung adenocarcinoma via STAT3/Jab1-PD-L1 signalling[J]. Cell Communication and Signaling, 2022, 20(1): 121-132. doi: 10.1186/s12964-022-00934-z
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