Curated Papers > High-Impact Authoritative Literature on "Tumor Microenvironment"

Neutrophils in the Tumor Microenvironment.

Literature Information

DOI	10.1016/j.it.2015.11.008
PMID	26700397
Journal	Trends in immunology
Impact Factor	13.9
JCR Quartile	Q1
Publication Year	2016
Times Cited	321
Keywords	Neutrophils, Tumor Microenvironment, Chronic Inflammation
Literature Type	Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
ISSN	1471-4906
Pages	41-52
Issue	37(1)
Authors	Davalyn R Powell, Anna Huttenlocher

TL;DR

This review explores the dual roles of neutrophils in the tumor microenvironment, highlighting their involvement in both promoting and inhibiting cancer progression through mechanisms of recruitment and resolution during tissue damage. The findings underscore the complexity of neutrophil behavior in chronic inflammation and suggest critical areas for future research to clarify their impact on cancer dynamics.

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Neutrophils · Tumor Microenvironment · Chronic Inflammation

Abstract

Neutrophils are the first responders to sites of acute tissue damage and infection. Recent studies suggest that in addition to neutrophil apoptosis, resolution of neutrophil inflammation at wounds can be mediated by reverse migration from tissues and transmigration back into the vasculature. In settings of chronic inflammation, neutrophils persist in tissues, and this persistence has been associated with cancer progression. However, the role of neutrophils in the tumor microenvironment remains controversial, with evidence for both pro- and anti-tumor roles. Here we review the mechanisms that regulate neutrophil recruitment and resolution at sites of tissue damage, with a specific focus on the tumor microenvironment. We discuss the current understanding as to how neutrophils alter the tumor microenvironment to support or hinder cancer progression, and in this context outline gaps in understanding and important areas of inquiry.

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Primary Questions Addressed

1. What specific mechanisms allow neutrophils to influence tumor progression in the microenvironment?
2. How do neutrophils interact with other immune cells within the tumor microenvironment to modulate their functions?
3. In what ways might the persistence of neutrophils in tissues contribute to chronic inflammation and cancer development?
4. What are the implications of neutrophil apoptosis and reverse migration for therapeutic strategies targeting tumor microenvironments?
5. How do different types of tumors affect the behavior and role of neutrophils in their microenvironments?

Key Findings

Research Background and Objectives

Neutrophils are the most abundant type of white blood cells and play a critical role in the immune response to infection and tissue damage. Recent findings indicate that neutrophils can have dual roles in cancer, both promoting and inhibiting tumor progression. This review aims to explore the mechanisms governing neutrophil behavior in the tumor microenvironment, including their recruitment, polarization, and effects on cancer progression, while identifying knowledge gaps and future research directions.

Main Methods/Materials/Experimental Design

The authors conducted a comprehensive review of existing literature, focusing on the recruitment mechanisms of neutrophils to tumors and their interactions with the tumor microenvironment. Key aspects include:

1. Neutrophil Recruitment Signals: Various chemokines, cytokines, and damage-associated molecular patterns (DAMPs) mediate neutrophil recruitment to tissues.
2. Neutrophil Polarization: Neutrophils can be polarized into either pro-tumor (N2) or anti-tumor (N1) phenotypes based on environmental cues.
3. Experimental Models: The review discusses findings from mouse models and zebrafish, which provide insights into neutrophil dynamics in cancer.

Key Results and Findings

1. Recruitment Mechanisms: Neutrophils are attracted to tumors by various signals, including chemokines like CXCL5 and CXCL8, which correlate with poor patient prognosis.
2. Dual Roles: Neutrophils can either promote tumor growth through angiogenesis and immune suppression or enhance anti-tumor immunity depending on their polarization.
3. Neutrophil Extracellular Traps (NETs): The formation of NETs can enhance tumor cell proliferation and metastasis, complicating the understanding of neutrophil roles in cancer.

Main Conclusions/Significance/Innovation

The review underscores the complexity of neutrophil functions in cancer, highlighting their potential as both therapeutic targets and biomarkers. The identification of neutrophil polarization and the mechanisms driving their behavior in the tumor microenvironment could lead to novel therapeutic strategies aimed at modulating neutrophil functions to improve cancer treatment outcomes.

Research Limitations and Future Directions

1. Context-Dependent Roles: The role of neutrophils in cancer is highly context-dependent, varying with tumor type and stage.
2. Need for Mechanistic Studies: Further research is needed to elucidate the precise mechanisms driving neutrophil polarization and their interactions with other immune cells.
3. Therapeutic Targeting: Future studies should focus on developing strategies to promote anti-tumor neutrophil phenotypes or enhance their resolution from tumors to mitigate chronic inflammation.

Summary Table

Aspect	Details
Neutrophil Roles	Pro-tumor (N2) vs. Anti-tumor (N1)
Recruitment Signals	Chemokines (CXCL5, CXCL8), Cytokines (IL-17), DAMPs
Key Findings	Neutrophils can enhance or inhibit tumor progression
Future Directions	Investigate neutrophil polarization mechanisms

References

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2. IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment. - Luciana Benevides;Denise Morais da Fonseca;Paula Barbim Donate;Daniel Guimarães Tiezzi;Daniel D De Carvalho;Jurandyr M de Andrade;Gislaine A Martins;João S Silva - Cancer research (2015)
3. Neutrophil-delivered myeloperoxidase dampens the hydrogen peroxide burst after tissue wounding in zebrafish. - Luke Pase;Judith E Layton;Christine Wittmann;Felix Ellett;Cameron J Nowell;Constantino Carlos Reyes-Aldasoro;Sony Varma;Kelly L Rogers;Chris J Hall;M Cristina Keightley;Philip S Crosier;Clemens Grabher;Joan K Heath;Stephen A Renshaw;Graham J Lieschke - Current biology : CB (2012)
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9. Neutrophil extracellular traps in cancer progression. - Jonathan Cools-Lartigue;Jonathan Spicer;Sara Najmeh;Lorenzo Ferri - Cellular and molecular life sciences : CMLS (2014)
10. VEGF-A recruits a proangiogenic MMP-9-delivering neutrophil subset that induces angiogenesis in transplanted hypoxic tissue. - Gustaf Christoffersson;Evelina Vågesjö;Jennifer Vandooren;Majken Lidén;Sara Massena;Rachel B Reinert;Marcela Brissova;Alvin C Powers;Ghislain Opdenakker;Mia Phillipson - Blood (2012)

Literatures Citing This Work

1. Postoperative Systemic Inflammatory Response, Complication Severity, and Survival Following Surgery for Colorectal Cancer. - Stephen T McSorley;David G Watt;Paul G Horgan;Donald C McMillan - Annals of surgical oncology (2016)
2. Key mechanisms governing resolution of lung inflammation. - C T Robb;K H Regan;D A Dorward;A G Rossi - Seminars in immunopathology (2016)
3. Neutrophils drive accelerated tumor progression in the collagen-dense mammary tumor microenvironment. - María G García-Mendoza;David R Inman;Suzanne M Ponik;Justin J Jeffery;Dagna S Sheerar;Rachel R Van Doorn;Patricia J Keely - Breast cancer research : BCR (2016)
4. Tumor-Derived CXCL1 Promotes Lung Cancer Growth via Recruitment of Tumor-Associated Neutrophils. - Ming Yuan;Ha Zhu;Junfang Xu;Yuanyuan Zheng;Xuetao Cao;Qiuyan Liu - Journal of immunology research (2016)
5. Herpesvirus-Associated Lymphadenitis Distorts Fibroblastic Reticular Cell Microarchitecture and Attenuates CD8 T Cell Responses to Neurotropic Infection in Mice Lacking the STING-IFNα/β Defense Pathways. - Derek J Royer;Christopher D Conrady;Daniel J J Carr - Journal of immunology (Baltimore, Md. : 1950) (2016)
6. The dual role of complement in cancer and its implication in anti-tumor therapy. - Ioannis Kourtzelis;Stavros Rafail - Annals of translational medicine (2016)
7. How cancer cells dictate their microenvironment: present roles of extracellular vesicles. - Yutaka Naito;Yusuke Yoshioka;Yusuke Yamamoto;Takahiro Ochiya - Cellular and molecular life sciences : CMLS (2017)
8. Monitoring of the Immune Dysfunction in Cancer Patients. - Saskia J A M Santegoets;Marij J P Welters;Sjoerd H van der Burg - Vaccines (2016)
9. Neutrophil plasticity enables the development of pathological microenvironments: implications for cystic fibrosis airway disease. - Camilla Margaroli;Rabindra Tirouvanziam - Molecular and cellular pediatrics (2016)
10. A Strong Neutrophil Elastase Proteolytic Fingerprint Marks the Carcinoma Tumor Proteome. - Michał Kistowski;Janusz Dębski;Jakub Karczmarski;Agnieszka Paziewska;Jacek Olędzki;Michał Mikula;Jerzy Ostrowski;Michał Dadlez - Molecular & cellular proteomics : MCP (2017)

... (311 more literatures)

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