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Effects of Nivolumab and Ipilimumab on the suppression of cisplatin resistant small cell lung cancer cells

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Abstract

Background

Small cell lung cancer (SCLC) accounts for nearly 10–15% of all lung cancer cases. Although many chemotherapy drugs, such as cisplatin and etoposide, were approved as primary therapy for SCLC patients, the prognosis is poor. In this study, we aimed to explore novel therapeutic strategy against SCLC.

Methods

Two SCLC cell lines, LTEP-P and LTEP-P/DDP1.0, were treated with cisplatin, in the absence or presence of Nivolumab + Ipilimumab combination, and the cell viability was measured. Tumor size and mouse survival rate were examined upon different drug treatments. Protein levels of PD-1 and CTLA4 were detected in normal and SCLC cells by Western blot. Cellular cytotoxicity induced by T lymphocytes was measured by thymidine incorporation assay. Tumor infiltrated T cell populations from LTEP-P and LTEP/DDP1.0 tumor-bearing mice were analyzed by flow cytometry.

Results

LTEP-P cells, but not LTEP/DDP1.0 cells, exhibited decreased cell viability upon cisplatin, Nivolumab and Ipilimumab combinational treatment. T lymphocytes significantly inhibited the growth of LTEP-P cells in the presence of nivolumab and ipilimumab. The combinational therapy improved survival rate and inhibited tumor growth in LTEP-P tumor-bearing mice, but showed no effect on LTEP/DDP1.0 tumor-bearing mice. Nivolumab and Ipilimumab synergized with cisplatin in increasing CD8 + and CD4 + T cell population, while decreasing Treg population in LTEP-P tumor-bearing mice.

Conclusions

The combinational therapy by cisplatin, Nivolumab and Ipilimumab could be an effective strategy against LTEP-P cells, accompanied with increased cytotoxic T cell populations, but has no significant effect against DDP-resistant lung adenocarcinoma cells.

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Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

This study was supported by Cangzhou Key R&D Project (204106180).

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Authors and Affiliations

  1. Department of pulmonary and Critical Care Medicine ward II, Cangzhou Central Hospital, Xinhua West Road, 061000, Cangzhou, Hebei, China

    Wei Chi, Lianyong Zhang, Xue Wang, Jingjing Li, Fei Li & Qianyun Zhang

  2. Department of Geriatrics, Cangzhou Central Hospital, 061000, Cangzhou, Hebei, China

    Yuxia Ma

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  1. Wei Chi
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Contributions

Qianyun Zhang designed and supervised the study. Fei Li and Yuxia Ma collected the data. Xue Wang, Jingjing Li and Lianyong Zhang performed experiments. Lianyong Zhang analysed data. Wei Chi wrote the manuscript and manuscript revisions. All authors read and approved the final manuscript.

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Correspondence to Qianyun Zhang.

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Chi, W., Zhang, L., Wang, X. et al. Effects of Nivolumab and Ipilimumab on the suppression of cisplatin resistant small cell lung cancer cells. Invest New Drugs 40, 709–717 (2022). https://doi.org/10.1007/s10637-022-01243-5

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