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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 7/2023

Open Access 28-02-2023 | Glioblastoma | Research

LILRB2-containing small extracellular vesicles from glioblastoma promote tumor progression by promoting the formation and expansion of myeloid-derived suppressor cells

Authors: Peitao Wu, Yuhang Guo, Li Xiao, Jiaqi Yuan, Chao Tang, Jun Dong, Zhiyuan Qian

Published in: Cancer Immunology, Immunotherapy | Issue 7/2023

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Abstract

Background

Leukocyte immunoglobulin-like receptor subfamily B2 (LILRB2) was reported to be an inhibitory molecule with suppressive functions. sEVs mediate communication between cancer cells and other cells. However, the existence of LILRB2 on sEVs in circulation and the function of sEVs-LILRB2 are still unknown. This study aims to investigate the role of LILRB2 in GBM and determine how LILRB2 in sEVs regulates tumor immunity.

Methods

LILRB2 expression in normal brain and GBM tissues was detected by immunohistochemistry, and the effect of LILRB2 on prognosis was evaluated in an orthotopic brain tumor model. Next, a subcutaneous tumor model was constructed to evaluate the function of pirb in vivo. The immune cells in the tumor sites and spleen were detected by immunofluorescence staining and flow cytometry. Then, the presence of pirb in sEVs was confirmed by WB. The percentage of immune cells after incubation with sEVs from GL261 (GL261-sEVs) or sEVs from GL261-pirb+ (GL261-sEVs-pirb) was detected by flow cytometry. Then, the effect of pirb on sEVs was evaluated by a tumor-killing assay and proliferation assay. Finally, subcutaneous tumor models were constructed to evaluate the function of pirb on sEVs.

Results

LILRB2 was overexpressed in human GBM tissue and was closely related to an immunosuppressive TME in GBM. Then, a protumor ability of LILRB2 was observed in subcutaneous tumor models, which was related to lower CD8 + T cells and higher MDSCs (myeloid-derived suppressor cells) in the tumor and spleen compared to those of the control group. Next, we found that pirb on sEVs (sEVs-pirb) inhibits the function of CD8 + T cells by promoting the formation and expansion of MDSCs. Furthermore, the protumor function of sEVs-pirb was demonstrated in subcutaneous tumor models.

Conclusion

We discovered that LILRB2/pirb can be transmitted between GBM cells via sEVs and that pirb on sEVs induces the formation and expansion of MDSCs. The induced MDSCs facilitate the formation of an immunosuppressive TME.

Graphical Abstract

Appendix
Available only for authorised users
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Metadata
Title
LILRB2-containing small extracellular vesicles from glioblastoma promote tumor progression by promoting the formation and expansion of myeloid-derived suppressor cells
Authors
Peitao Wu
Yuhang Guo
Li Xiao
Jiaqi Yuan
Chao Tang
Jun Dong
Zhiyuan Qian
Publication date
28-02-2023
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 7/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-023-03395-6

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