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Frontiers in Pharmacology: Review Manuscript Targeting of the Neutrophil as an Adjunctive Strategy in Non-Small Cell Lung Cancer

Lung cancer remains the leading cause of cancer mortality in the United States, with non-small cell lung cancer (NSCLC) accounting for around 85% of cases. Of particular concern is the poor responsiveness of this malignancy to therapy, resulting in a very low 5-year survival rate (17.4%) and a promi...

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Autores principales: Anderson, Ronald, Blidner, Ada Gabriela, Rapoport, Bernardo Leon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218630/
https://www.ncbi.nlm.nih.gov/pubmed/34168563
http://dx.doi.org/10.3389/fphar.2021.676399
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author Anderson, Ronald
Blidner, Ada Gabriela
Rapoport, Bernardo Leon
author_facet Anderson, Ronald
Blidner, Ada Gabriela
Rapoport, Bernardo Leon
author_sort Anderson, Ronald
collection PubMed
description Lung cancer remains the leading cause of cancer mortality in the United States, with non-small cell lung cancer (NSCLC) accounting for around 85% of cases. Of particular concern is the poor responsiveness of this malignancy to therapy, resulting in a very low 5-year survival rate (17.4%) and a prominent tendency to progress to metastatic disease. A number of very recent studies, both pre-clinical and clinical, have implicated the neutrophil in both the pathogenesis and unsatisfactory response to therapy of NSCLC. In this context, movement of neutrophils into the tumor microenvironment (TME) is a common feature of NSCLC. Indeed neutrophils are the dominant type of immune cell in the NSCLC TME, creating a highly immunosuppressive milieu that is not only conducive to tumor growth and spread, but also represents a significant obstacle to the success of anti-tumor therapy, especially novel immunotherapies. The clinically relevant adverse impact of a neutrophil predominance both systemically and in the TME of patients with NSCLC is underscored by the negative prognostic value of both a persistent neutrophilia and, in particular, a high (≥5) neutrophil:lymphocyte ratio. On a more positive note, however, recognition of the involvement of the neutrophil in both the pathophysiology of NSCLC and treatment failure has enabled identification of neutrophil-targeted strategies that have the potential to serve as adjuncts to standard anti-cancer therapies, including immunotherapy. These strategies together with a consideration of the immunosuppressive, pro-tumorigenic properties of the neutrophil represent the major thrusts of this review.
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spelling pubmed-82186302021-06-23 Frontiers in Pharmacology: Review Manuscript Targeting of the Neutrophil as an Adjunctive Strategy in Non-Small Cell Lung Cancer Anderson, Ronald Blidner, Ada Gabriela Rapoport, Bernardo Leon Front Pharmacol Pharmacology Lung cancer remains the leading cause of cancer mortality in the United States, with non-small cell lung cancer (NSCLC) accounting for around 85% of cases. Of particular concern is the poor responsiveness of this malignancy to therapy, resulting in a very low 5-year survival rate (17.4%) and a prominent tendency to progress to metastatic disease. A number of very recent studies, both pre-clinical and clinical, have implicated the neutrophil in both the pathogenesis and unsatisfactory response to therapy of NSCLC. In this context, movement of neutrophils into the tumor microenvironment (TME) is a common feature of NSCLC. Indeed neutrophils are the dominant type of immune cell in the NSCLC TME, creating a highly immunosuppressive milieu that is not only conducive to tumor growth and spread, but also represents a significant obstacle to the success of anti-tumor therapy, especially novel immunotherapies. The clinically relevant adverse impact of a neutrophil predominance both systemically and in the TME of patients with NSCLC is underscored by the negative prognostic value of both a persistent neutrophilia and, in particular, a high (≥5) neutrophil:lymphocyte ratio. On a more positive note, however, recognition of the involvement of the neutrophil in both the pathophysiology of NSCLC and treatment failure has enabled identification of neutrophil-targeted strategies that have the potential to serve as adjuncts to standard anti-cancer therapies, including immunotherapy. These strategies together with a consideration of the immunosuppressive, pro-tumorigenic properties of the neutrophil represent the major thrusts of this review. Frontiers Media S.A. 2021-06-08 /pmc/articles/PMC8218630/ /pubmed/34168563 http://dx.doi.org/10.3389/fphar.2021.676399 Text en Copyright © 2021 Anderson, Blidner and Rapoport. 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 Pharmacology
Anderson, Ronald
Blidner, Ada Gabriela
Rapoport, Bernardo Leon
Frontiers in Pharmacology: Review Manuscript Targeting of the Neutrophil as an Adjunctive Strategy in Non-Small Cell Lung Cancer
title Frontiers in Pharmacology: Review Manuscript Targeting of the Neutrophil as an Adjunctive Strategy in Non-Small Cell Lung Cancer
title_full Frontiers in Pharmacology: Review Manuscript Targeting of the Neutrophil as an Adjunctive Strategy in Non-Small Cell Lung Cancer
title_fullStr Frontiers in Pharmacology: Review Manuscript Targeting of the Neutrophil as an Adjunctive Strategy in Non-Small Cell Lung Cancer
title_full_unstemmed Frontiers in Pharmacology: Review Manuscript Targeting of the Neutrophil as an Adjunctive Strategy in Non-Small Cell Lung Cancer
title_short Frontiers in Pharmacology: Review Manuscript Targeting of the Neutrophil as an Adjunctive Strategy in Non-Small Cell Lung Cancer
title_sort frontiers in pharmacology: review manuscript targeting of the neutrophil as an adjunctive strategy in non-small cell lung cancer
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218630/
https://www.ncbi.nlm.nih.gov/pubmed/34168563
http://dx.doi.org/10.3389/fphar.2021.676399
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