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PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma
While pulmonary ILC2s represent one of the major tissue-resident innate lymphoid cell populations at steady state and are key drivers of cytokine secretion in their occupational niche, their role in pulmonary cancer progression remains unclear. As the programmed cell death protein-1 (PD-1) plays a m...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438316/ https://www.ncbi.nlm.nih.gov/pubmed/34531874 http://dx.doi.org/10.3389/fimmu.2021.733136 |
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author | Howard, Emily Hurrell, Benjamin P. Helou, Doumet Georges Quach, Christine Painter, Jacob D. Shafiei-Jahani, Pedram Fung, Marshall Gill, Parkash S. Soroosh, Pejman Sharpe, Arlene H. Akbari, Omid |
author_facet | Howard, Emily Hurrell, Benjamin P. Helou, Doumet Georges Quach, Christine Painter, Jacob D. Shafiei-Jahani, Pedram Fung, Marshall Gill, Parkash S. Soroosh, Pejman Sharpe, Arlene H. Akbari, Omid |
author_sort | Howard, Emily |
collection | PubMed |
description | While pulmonary ILC2s represent one of the major tissue-resident innate lymphoid cell populations at steady state and are key drivers of cytokine secretion in their occupational niche, their role in pulmonary cancer progression remains unclear. As the programmed cell death protein-1 (PD-1) plays a major role in cancer immunotherapy and immunoregulatory properties, here we investigate the specific effect of PD-1 inhibition on ILC2s during pulmonary B16 melanoma cancer metastasis. We demonstrate that PD-1 inhibition on ILC2s suppresses B16 tumor growth. Further, PD-1 inhibition upregulates pulmonary ILC2-derived TNF-α production, a cytotoxic cytokine that directly induces cell death in B16 cells, independent of adaptive immunity. Together, these results highlight the importance of ILC2s and their anti-tumor role in pulmonary B16 cancer progression during PD-1 inhibitory immunotherapy. |
format | Online Article Text |
id | pubmed-8438316 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84383162021-09-15 PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma Howard, Emily Hurrell, Benjamin P. Helou, Doumet Georges Quach, Christine Painter, Jacob D. Shafiei-Jahani, Pedram Fung, Marshall Gill, Parkash S. Soroosh, Pejman Sharpe, Arlene H. Akbari, Omid Front Immunol Immunology While pulmonary ILC2s represent one of the major tissue-resident innate lymphoid cell populations at steady state and are key drivers of cytokine secretion in their occupational niche, their role in pulmonary cancer progression remains unclear. As the programmed cell death protein-1 (PD-1) plays a major role in cancer immunotherapy and immunoregulatory properties, here we investigate the specific effect of PD-1 inhibition on ILC2s during pulmonary B16 melanoma cancer metastasis. We demonstrate that PD-1 inhibition on ILC2s suppresses B16 tumor growth. Further, PD-1 inhibition upregulates pulmonary ILC2-derived TNF-α production, a cytotoxic cytokine that directly induces cell death in B16 cells, independent of adaptive immunity. Together, these results highlight the importance of ILC2s and their anti-tumor role in pulmonary B16 cancer progression during PD-1 inhibitory immunotherapy. Frontiers Media S.A. 2021-08-31 /pmc/articles/PMC8438316/ /pubmed/34531874 http://dx.doi.org/10.3389/fimmu.2021.733136 Text en Copyright © 2021 Howard, Hurrell, Helou, Quach, Painter, Shafiei-Jahani, Fung, Gill, Soroosh, Sharpe and Akbari 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 Howard, Emily Hurrell, Benjamin P. Helou, Doumet Georges Quach, Christine Painter, Jacob D. Shafiei-Jahani, Pedram Fung, Marshall Gill, Parkash S. Soroosh, Pejman Sharpe, Arlene H. Akbari, Omid PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma |
title | PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma |
title_full | PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma |
title_fullStr | PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma |
title_full_unstemmed | PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma |
title_short | PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma |
title_sort | pd-1 blockade on tumor microenvironment-resident ilc2s promotes tnf-α production and restricts progression of metastatic melanoma |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438316/ https://www.ncbi.nlm.nih.gov/pubmed/34531874 http://dx.doi.org/10.3389/fimmu.2021.733136 |
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