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Discover Oncology
Published in: Discover Oncology 1/2023

Open Access 01-12-2023 | Breast Cancer | Research

GPR81-mediated reprogramming of glucose metabolism contributes to the immune landscape in breast cancer

Authors: Xiaofeng li, Yiwen Chen, Ting Wang, Zifan Liu, Guotao Yin, Ziyang Wang, Chunxiao Sui, Lei Zhu, Wei Chen

Published in: Discover Oncology | Issue 1/2023

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Abstract

Background

Local tumor microenvironment (TME) plays a crucial role in immunotherapy for breast cancer (BC). Whereas, the molecular mechanism responsible for the crosstalk between BC cells and surrounding immune cells remains unclear. The present study aimed to determine the interplay between GPR81-mediated glucometabolic reprogramming of BC and the immune landscape in TME.

Materials and Methods

Immunohistochemistry (IHC) assay was first performed to evaluate the association between GPR81 and the immune landscape. Then, several stable BC cell lines with down-regulated GPR81 expression were established to directly identify the role of GPR81 in glucometabolic reprogramming, and western blotting assay was used to detect the underlying molecular mechanism. Finally, a transwell co-culture system confirmed the crosstalk between glucometabolic regulation mediated by GPR81 in BC and induced immune attenuation.

Results

IHC analysis demonstrated that the representation of infiltrating CD8+ T cells and FOXP3+ T cells were dramatically higher in BC with a triple negative (TN) subtype in comparison with that with a non-TN subtype (P < 0.001). Additionally, the ratio of infiltrating CD8+ to FOXP3+ T cells was significantly negatively associated with GPR81 expression in BC with a TN subtype (P < 0.001). Furthermore, GPR81 was found to be substantially correlated with the glycolytic capability (P < 0.001) of BC cells depending on a Hippo-YAP signaling pathway (P < 0.001). In the transwell co-culture system, GPR81-mediated reprogramming of glucose metabolism in BC significantly contributed to a decreased proportion of CD8+ T (P < 0.001) and an increased percentage of FOXP3+ T (P < 0.001) in the co-cultured lymphocytes.

Conclusion

Glucometabolic reprogramming through a GPR81-mediated Hippo-YAP signaling pathway was responsible for the distinct immune landscape in BC. GPR81 was a potential biomarker to stratify patients before immunotherapy to improve BC’s clinical prospect.
Appendix
Available only for authorised users
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Metadata
Title
GPR81-mediated reprogramming of glucose metabolism contributes to the immune landscape in breast cancer
Authors
Xiaofeng li
Yiwen Chen
Ting Wang
Zifan Liu
Guotao Yin
Ziyang Wang
Chunxiao Sui
Lei Zhu
Wei Chen
Publication date
01-12-2023
Publisher
Springer US
Published in
Discover Oncology / Issue 1/2023
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-023-00709-z

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