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GM-CSF: A Double-Edged Sword in Cancer Immunotherapy
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that drives the generation of myeloid cell subsets including neutrophils, monocytes, macrophages, and dendritic cells in response to stress, infections, and cancers. By modulating the functions of innate immune cells that serve...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294178/ https://www.ncbi.nlm.nih.gov/pubmed/35865534 http://dx.doi.org/10.3389/fimmu.2022.901277 |
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author | Kumar, Anil Taghi Khani, Adeleh Sanchez Ortiz, Ashly Swaminathan, Srividya |
author_facet | Kumar, Anil Taghi Khani, Adeleh Sanchez Ortiz, Ashly Swaminathan, Srividya |
author_sort | Kumar, Anil |
collection | PubMed |
description | Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that drives the generation of myeloid cell subsets including neutrophils, monocytes, macrophages, and dendritic cells in response to stress, infections, and cancers. By modulating the functions of innate immune cells that serve as a bridge to activate adaptive immune responses, GM-CSF globally impacts host immune surveillance under pathologic conditions. As with other soluble mediators of immunity, too much or too little GM-CSF has been found to promote cancer aggressiveness. While too little GM-CSF prevents the appropriate production of innate immune cells and subsequent activation of adaptive anti-cancer immune responses, too much of GM-CSF can exhaust immune cells and promote cancer growth. The consequences of GM-CSF signaling in cancer progression are a function of the levels of GM-CSF, the cancer type, and the tumor microenvironment. In this review, we first discuss the secretion of GM-CSF, signaling downstream of the GM-CSF receptor, and GM-CSF’s role in modulating myeloid cell homeostasis. We then outline GM-CSF’s anti-tumorigenic and pro-tumorigenic effects both on the malignant cells and on the non-malignant immune and other cells in the tumor microenvironment. We provide examples of current clinical and preclinical strategies that harness GM-CSF’s anti-cancer potential while minimizing its deleterious effects. We describe the challenges in achieving the Goldilocks effect during administration of GM-CSF-based therapies to patients with cancer. Finally, we provide insights into how technologies that map the immune microenvironment spatially and temporally may be leveraged to intelligently harness GM-CSF for treatment of malignancies. |
format | Online Article Text |
id | pubmed-9294178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92941782022-07-20 GM-CSF: A Double-Edged Sword in Cancer Immunotherapy Kumar, Anil Taghi Khani, Adeleh Sanchez Ortiz, Ashly Swaminathan, Srividya Front Immunol Immunology Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that drives the generation of myeloid cell subsets including neutrophils, monocytes, macrophages, and dendritic cells in response to stress, infections, and cancers. By modulating the functions of innate immune cells that serve as a bridge to activate adaptive immune responses, GM-CSF globally impacts host immune surveillance under pathologic conditions. As with other soluble mediators of immunity, too much or too little GM-CSF has been found to promote cancer aggressiveness. While too little GM-CSF prevents the appropriate production of innate immune cells and subsequent activation of adaptive anti-cancer immune responses, too much of GM-CSF can exhaust immune cells and promote cancer growth. The consequences of GM-CSF signaling in cancer progression are a function of the levels of GM-CSF, the cancer type, and the tumor microenvironment. In this review, we first discuss the secretion of GM-CSF, signaling downstream of the GM-CSF receptor, and GM-CSF’s role in modulating myeloid cell homeostasis. We then outline GM-CSF’s anti-tumorigenic and pro-tumorigenic effects both on the malignant cells and on the non-malignant immune and other cells in the tumor microenvironment. We provide examples of current clinical and preclinical strategies that harness GM-CSF’s anti-cancer potential while minimizing its deleterious effects. We describe the challenges in achieving the Goldilocks effect during administration of GM-CSF-based therapies to patients with cancer. Finally, we provide insights into how technologies that map the immune microenvironment spatially and temporally may be leveraged to intelligently harness GM-CSF for treatment of malignancies. Frontiers Media S.A. 2022-07-05 /pmc/articles/PMC9294178/ /pubmed/35865534 http://dx.doi.org/10.3389/fimmu.2022.901277 Text en Copyright © 2022 Kumar, Taghi Khani, Sanchez Ortiz and Swaminathan 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 Kumar, Anil Taghi Khani, Adeleh Sanchez Ortiz, Ashly Swaminathan, Srividya GM-CSF: A Double-Edged Sword in Cancer Immunotherapy |
title | GM-CSF: A Double-Edged Sword in Cancer Immunotherapy |
title_full | GM-CSF: A Double-Edged Sword in Cancer Immunotherapy |
title_fullStr | GM-CSF: A Double-Edged Sword in Cancer Immunotherapy |
title_full_unstemmed | GM-CSF: A Double-Edged Sword in Cancer Immunotherapy |
title_short | GM-CSF: A Double-Edged Sword in Cancer Immunotherapy |
title_sort | gm-csf: a double-edged sword in cancer immunotherapy |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294178/ https://www.ncbi.nlm.nih.gov/pubmed/35865534 http://dx.doi.org/10.3389/fimmu.2022.901277 |
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