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Notch Signaling as a Regulator of the Tumor Immune Response: To Target or Not To Target?

The Notch signaling pathway regulates important cellular processes involved in stem cell maintenance, proliferation, development, survival, and inflammation. These responses to Notch signaling involving both canonical and non-canonical pathways can be spatially and temporally variable and are highly...

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Autores principales: Janghorban, Mahnaz, Xin, Li, Rosen, Jeffrey M., Zhang, Xiang H.-F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055003/
https://www.ncbi.nlm.nih.gov/pubmed/30061899
http://dx.doi.org/10.3389/fimmu.2018.01649
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author Janghorban, Mahnaz
Xin, Li
Rosen, Jeffrey M.
Zhang, Xiang H.-F.
author_facet Janghorban, Mahnaz
Xin, Li
Rosen, Jeffrey M.
Zhang, Xiang H.-F.
author_sort Janghorban, Mahnaz
collection PubMed
description The Notch signaling pathway regulates important cellular processes involved in stem cell maintenance, proliferation, development, survival, and inflammation. These responses to Notch signaling involving both canonical and non-canonical pathways can be spatially and temporally variable and are highly cell-type dependent. Notch signaling can elicit opposite effects in regulating tumorigenicity (tumor-promoting versus tumor-suppressing function) as well as controlling immune cell responses. In various cancer types, Notch signaling elicits a “cancer stem cell (CSC)” phenotype that results in decreased proliferation, but resistance to various therapies, hence potentially contributing to cell dormancy and relapse. CSCs can reshape their niche by releasing paracrine factors and inflammatory cytokines, and the niche in return can support their quiescence and resistance to therapies as well as the immune response. Moreover, Notch signaling is one of the key regulators of hematopoiesis, immune cell differentiation, and inflammation and is implicated in various autoimmune diseases, carcinogenesis (leukemia), and tumor-induced immunosuppression. Notch can control the fate of various T cell types, including Th1, Th2, and the regulatory T cells (Tregs), and myeloid cells including macrophages, dendritic cells, and myeloid-derived suppressor cells (MDSCs). Both MDSCs and Tregs play an important role in supporting tumor cells (and CSCs) and in evading the immune response. In this review, we will discuss how Notch signaling regulates multiple aspects of the tumor-promoting environment by elucidating its role in CSCs, hematopoiesis, normal immune cell differentiation, and subsequently in tumor-supporting immunogenicity.
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spelling pubmed-60550032018-07-30 Notch Signaling as a Regulator of the Tumor Immune Response: To Target or Not To Target? Janghorban, Mahnaz Xin, Li Rosen, Jeffrey M. Zhang, Xiang H.-F. Front Immunol Immunology The Notch signaling pathway regulates important cellular processes involved in stem cell maintenance, proliferation, development, survival, and inflammation. These responses to Notch signaling involving both canonical and non-canonical pathways can be spatially and temporally variable and are highly cell-type dependent. Notch signaling can elicit opposite effects in regulating tumorigenicity (tumor-promoting versus tumor-suppressing function) as well as controlling immune cell responses. In various cancer types, Notch signaling elicits a “cancer stem cell (CSC)” phenotype that results in decreased proliferation, but resistance to various therapies, hence potentially contributing to cell dormancy and relapse. CSCs can reshape their niche by releasing paracrine factors and inflammatory cytokines, and the niche in return can support their quiescence and resistance to therapies as well as the immune response. Moreover, Notch signaling is one of the key regulators of hematopoiesis, immune cell differentiation, and inflammation and is implicated in various autoimmune diseases, carcinogenesis (leukemia), and tumor-induced immunosuppression. Notch can control the fate of various T cell types, including Th1, Th2, and the regulatory T cells (Tregs), and myeloid cells including macrophages, dendritic cells, and myeloid-derived suppressor cells (MDSCs). Both MDSCs and Tregs play an important role in supporting tumor cells (and CSCs) and in evading the immune response. In this review, we will discuss how Notch signaling regulates multiple aspects of the tumor-promoting environment by elucidating its role in CSCs, hematopoiesis, normal immune cell differentiation, and subsequently in tumor-supporting immunogenicity. Frontiers Media S.A. 2018-07-16 /pmc/articles/PMC6055003/ /pubmed/30061899 http://dx.doi.org/10.3389/fimmu.2018.01649 Text en Copyright © 2018 Janghorban, Xin, Rosen and Zhang. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Janghorban, Mahnaz
Xin, Li
Rosen, Jeffrey M.
Zhang, Xiang H.-F.
Notch Signaling as a Regulator of the Tumor Immune Response: To Target or Not To Target?
title Notch Signaling as a Regulator of the Tumor Immune Response: To Target or Not To Target?
title_full Notch Signaling as a Regulator of the Tumor Immune Response: To Target or Not To Target?
title_fullStr Notch Signaling as a Regulator of the Tumor Immune Response: To Target or Not To Target?
title_full_unstemmed Notch Signaling as a Regulator of the Tumor Immune Response: To Target or Not To Target?
title_short Notch Signaling as a Regulator of the Tumor Immune Response: To Target or Not To Target?
title_sort notch signaling as a regulator of the tumor immune response: to target or not to target?
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055003/
https://www.ncbi.nlm.nih.gov/pubmed/30061899
http://dx.doi.org/10.3389/fimmu.2018.01649
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