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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doaj-50dc191d8a6e4e9c95413d400e56b67b2021-09-10T05:59:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.734188734188The Recruitment of Neutrophils to the Tumor Microenvironment Is Regulated by Multiple MediatorsShuvasree SenGupta0Shuvasree SenGupta1Lauren E. Hein2Lauren E. Hein3Carole A. Parent4Carole A. Parent5Carole A. Parent6Carole A. Parent7Life Sciences Institute, University of Michigan, Ann Arbor, MI, United StatesDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, United StatesCancer Biology Graduate Program, University of Michigan Medical School, Ann Arbor, MI, United StatesRogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, United StatesLife Sciences Institute, University of Michigan, Ann Arbor, MI, United StatesDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, United StatesRogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesNeutrophils 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.734188/fullneutrophilstumor-associated neutrophils (TANs)chemokinesTGF-βEMTsecretory pathways |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuvasree SenGupta Shuvasree SenGupta Lauren E. Hein Lauren E. Hein Carole A. Parent Carole A. Parent Carole A. Parent Carole A. Parent |
spellingShingle |
Shuvasree SenGupta Shuvasree SenGupta Lauren E. Hein Lauren E. Hein Carole A. Parent Carole A. Parent Carole A. Parent Carole A. Parent The Recruitment of Neutrophils to the Tumor Microenvironment Is Regulated by Multiple Mediators Frontiers in Immunology neutrophils tumor-associated neutrophils (TANs) chemokines TGF-β EMT secretory pathways |
author_facet |
Shuvasree SenGupta Shuvasree SenGupta Lauren E. Hein Lauren E. Hein Carole A. Parent Carole A. Parent Carole A. Parent Carole A. Parent |
author_sort |
Shuvasree SenGupta |
title |
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_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_sort |
recruitment of neutrophils to the tumor microenvironment is regulated by multiple mediators |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-09-01 |
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. |
topic |
neutrophils tumor-associated neutrophils (TANs) chemokines TGF-β EMT secretory pathways |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.734188/full |
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