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LINC01119 encapsulated by cancer-associated adipocytes-derived exosomes promotes M2 polarization of macrophages to induce immune escape in ovarian cancer in a 3D co-culture cell-based model

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Abstract

Introduction

In the present study, we sought to clarify the role of LINC01119 delivered by cancer-associated adipocytes (CAAs)-derived exosomes (CAA-Exo) and its mechanistic actions in ovarian cancer (OC).

Materials and methods

The expression of LINC01119 was determined in OC, and the relationship between LINC01119 expression and the prognosis of OC patients was analyzed. Besides, 3D co-culture cell models were constructed using green fluorescent protein-labeled OC cells and red fluorescent protein-labeled mature adipocytes. Mature adipocytes were co-cultured with OC cells to induce CAA. Macrophages treated with CAA-Exo were co-cultured with SKOV3 cells following ectopic expression and depletion experiments of LINC01119 and SOCS5 to detect M2 polarization of macrophages, PD-L1 level, proliferation of CD3+ T cells, and cytotoxicity of T cells to SKOV3 cells.

Results

LINC01119 was elevated in the plasma Exo of OC patients, which was related to shorter overall survival in OC patients. LINC01119 expression was increased in CAA-Exo, which could upregulate SOCS5 in OC. Finally, CAA-Exo carrying LINC01119 induced M2 polarization of macrophages to promote immune escape in OC, as evidenced by inhibited CD3+ T cell proliferation, increased PD-L1 level, and attenuated T cell toxicity to SKOV3 cells.

Conclusion

In conclusion, the key findings of the current study demonstrated the promoting effects of CAA-Exo containing LINC01119 mediating SOCS5 on M2 polarization of macrophages and immune escape in OC.

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Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.

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Acknowledgements

Not applicable.

Funding

This study was supported by Medical Key Supporting Project of Suzhou City (no. SZFCXK202142); Key Projects of Medical and Health Science and Technology Plan of Suzhou Hi-tech Zone (2020Z008) and Suzhou Science and Technology Development Plan (no. SKJYD2021058).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, School of Medicine, Huzhou University, Huzhou, 313000, Zhejiang, China

    Qingling Zheng

  2. Department of Pathology, Suzhou Science and Technology Town Hospital, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153, Jiangsu, China

    Jin Zhang, Yanxiang Liu, Xin Dai, Xiuluan Du & Donghua Gu

  3. Department of Pathology, School of Medicine, Huzhou University, Huzhou, 313000, Zhejiang, China

    Weijia Dong

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  1. Qingling Zheng
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  7. Donghua Gu
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Contributions

QLZ, JZ and DHG designed the study. YXL, WJD, XD and XLD collated the data, carried out data analyses and produced the initial draft of the manuscript. QLZ, JZ and DHG contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

Corresponding author

Correspondence to Donghua Gu.

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Conflict of interest

The authors declare no conflict of interest.

Ethical statement

This study was approved by the Ethics Committee of Suzhou Science & Technology Town Hospital and the methods were carried out in accordance with the approved guidelines. All the patients have been informed and signed informed consent before the experiments.

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Supplementary Information

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12094_2023_3185_MOESM1_ESM.tif

Figure S1 Effect of M2 macrophage polarization inhibitors on immune escape of OC cells. A, PD-L1 protein level in SKOV3 cells measured by Western blot analysis. B, The cytotoxicity of T cells to SKOV3 cells detected by LDH release assay. C, CFSE-labeled T cell proliferation assessed by flow cytometry. ns p>0.05; **p<0.05; **p<0.01; ***p<0.001. All cell experiments were repeated three times (TIFF 20,761 KB)

Supplementary file2 (DOCX 21 KB)

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Zheng, Q., Zhang, J., Liu, Y. et al. LINC01119 encapsulated by cancer-associated adipocytes-derived exosomes promotes M2 polarization of macrophages to induce immune escape in ovarian cancer in a 3D co-culture cell-based model. Clin Transl Oncol 25, 3174–3187 (2023). https://doi.org/10.1007/s12094-023-03185-7

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  • DOI: https://doi.org/10.1007/s12094-023-03185-7

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