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The Recruitment of Neutrophils to the Tumor Microenvironment Is Regulated by Multiple Mediators

Neutrophils sense and migrate towards chemotactic factors released at sites of infection/inflammation and contain the affected area using a variety of effector mechanisms. Aside from these established immune defense functions, neutrophils are emerging as one of the key tumor-infiltrating immune cell...

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Autores principales: SenGupta, Shuvasree, Hein, Lauren E., Parent, Carole A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461236/
https://www.ncbi.nlm.nih.gov/pubmed/34567000
http://dx.doi.org/10.3389/fimmu.2021.734188
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author SenGupta, Shuvasree
Hein, Lauren E.
Parent, Carole A.
author_facet SenGupta, Shuvasree
Hein, Lauren E.
Parent, Carole A.
author_sort SenGupta, Shuvasree
collection PubMed
description Neutrophils sense and migrate towards chemotactic factors released at sites of infection/inflammation and contain the affected area using a variety of effector mechanisms. Aside from these established immune defense functions, neutrophils are emerging as one of the key tumor-infiltrating immune cells that influence cancer progression and metastasis. Neutrophil recruitment to the tumor microenvironment (TME) is mediated by multiple mediators including cytokines, chemokines, lipids, and growth factors that are secreted from cancer cells and cancer-associated stromal cells. However, the molecular mechanisms that underlie the expression and secretion of the different mediators from cancer cells and how neutrophils integrate these signals to reach and invade tumors remain unclear. Here, we discuss the possible role of the epithelial to mesenchymal transition (EMT) program, which is a well-established promoter of malignant potential in cancer, in regulating the expression and secretion of these key mediators. We also summarize and review our current understanding of the machineries that potentially control the secretion of the mediators from cancer cells, including the exocytic trafficking pathways, secretory autophagy, and extracellular vesicle-mediated secretion. We further reflect on possible mechanisms by which different mediators collaborate by integrating their signaling network, and particularly focus on TGF-β, a cytokine that is highly expressed in invasive tumors, and CXCR2 ligands, which are crucial neutrophil recruiting chemokines. Finally, we highlight gaps in the field and the need to expand current knowledge of the secretory machineries and cross-talks among mediators to develop novel neutrophil targeting strategies as effective therapeutic options in the treatment of cancer.
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spelling pubmed-84612362021-09-25 The Recruitment of Neutrophils to the Tumor Microenvironment Is Regulated by Multiple Mediators SenGupta, Shuvasree Hein, Lauren E. Parent, Carole A. Front Immunol Immunology Neutrophils sense and migrate towards chemotactic factors released at sites of infection/inflammation and contain the affected area using a variety of effector mechanisms. Aside from these established immune defense functions, neutrophils are emerging as one of the key tumor-infiltrating immune cells that influence cancer progression and metastasis. Neutrophil recruitment to the tumor microenvironment (TME) is mediated by multiple mediators including cytokines, chemokines, lipids, and growth factors that are secreted from cancer cells and cancer-associated stromal cells. However, the molecular mechanisms that underlie the expression and secretion of the different mediators from cancer cells and how neutrophils integrate these signals to reach and invade tumors remain unclear. Here, we discuss the possible role of the epithelial to mesenchymal transition (EMT) program, which is a well-established promoter of malignant potential in cancer, in regulating the expression and secretion of these key mediators. We also summarize and review our current understanding of the machineries that potentially control the secretion of the mediators from cancer cells, including the exocytic trafficking pathways, secretory autophagy, and extracellular vesicle-mediated secretion. We further reflect on possible mechanisms by which different mediators collaborate by integrating their signaling network, and particularly focus on TGF-β, a cytokine that is highly expressed in invasive tumors, and CXCR2 ligands, which are crucial neutrophil recruiting chemokines. Finally, we highlight gaps in the field and the need to expand current knowledge of the secretory machineries and cross-talks among mediators to develop novel neutrophil targeting strategies as effective therapeutic options in the treatment of cancer. Frontiers Media S.A. 2021-09-10 /pmc/articles/PMC8461236/ /pubmed/34567000 http://dx.doi.org/10.3389/fimmu.2021.734188 Text en Copyright © 2021 SenGupta, Hein and Parent 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
SenGupta, Shuvasree
Hein, Lauren E.
Parent, Carole A.
The Recruitment of Neutrophils to the Tumor Microenvironment Is Regulated by Multiple Mediators
title The Recruitment of Neutrophils to the Tumor Microenvironment Is Regulated by Multiple Mediators
title_full The Recruitment of Neutrophils to the Tumor Microenvironment Is Regulated by Multiple Mediators
title_fullStr The Recruitment of Neutrophils to the Tumor Microenvironment Is Regulated by Multiple Mediators
title_full_unstemmed The Recruitment of Neutrophils to the Tumor Microenvironment Is Regulated by Multiple Mediators
title_short The Recruitment of Neutrophils to the Tumor Microenvironment Is Regulated by Multiple Mediators
title_sort recruitment of neutrophils to the tumor microenvironment is regulated by multiple mediators
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461236/
https://www.ncbi.nlm.nih.gov/pubmed/34567000
http://dx.doi.org/10.3389/fimmu.2021.734188
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