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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2023

Open Access 01-12-2023 | Cancer Immunotherapy | Review

The Notch signaling pathway: a potential target for cancer immunotherapy

Authors: Xinxin Li, Xianchun Yan, Yufeng Wang, Balveen Kaur, Hua Han, Jianhua Yu

Published in: Journal of Hematology & Oncology | Issue 1/2023

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Abstract

Dysregulation of the Notch signaling pathway, which is highly conserved across species, can drive aberrant epigenetic modification, transcription, and translation. Defective gene regulation caused by dysregulated Notch signaling often affects networks controlling oncogenesis and tumor progression. Meanwhile, Notch signaling can modulate immune cells involved in anti- or pro-tumor responses and tumor immunogenicity. A comprehensive understanding of these processes can help with designing new drugs that target Notch signaling, thereby enhancing the effects of cancer immunotherapy. Here, we provide an up-to-date and comprehensive overview of how Notch signaling intrinsically regulates immune cells and how alterations in Notch signaling in tumor cells or stromal cells extrinsically regulate immune responses in the tumor microenvironment (TME). We also discuss the potential role of Notch signaling in tumor immunity mediated by gut microbiota. Finally, we propose strategies for targeting Notch signaling in cancer immunotherapy. These include oncolytic virotherapy combined with inhibition of Notch signaling, nanoparticles (NPs) loaded with Notch signaling regulators to specifically target tumor-associated macrophages (TAMs) to repolarize their functions and remodel the TME, combining specific and efficient inhibitors or activators of Notch signaling with immune checkpoint blockers (ICBs) for synergistic anti-tumor therapy, and implementing a customized and effective synNotch circuit system to enhance safety of chimeric antigen receptor (CAR) immune cells. Collectively, this review aims to summarize how Notch signaling intrinsically and extrinsically shapes immune responses to improve immunotherapy.
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Metadata
Title
The Notch signaling pathway: a potential target for cancer immunotherapy
Authors
Xinxin Li
Xianchun Yan
Yufeng Wang
Balveen Kaur
Hua Han
Jianhua Yu
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2023
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-023-01439-z

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