Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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
_version_ 1783752344975966208
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
work_keys_str_mv AT howardemily pd1blockadeontumormicroenvironmentresidentilc2spromotestnfaproductionandrestrictsprogressionofmetastaticmelanoma
AT hurrellbenjaminp pd1blockadeontumormicroenvironmentresidentilc2spromotestnfaproductionandrestrictsprogressionofmetastaticmelanoma
AT heloudoumetgeorges pd1blockadeontumormicroenvironmentresidentilc2spromotestnfaproductionandrestrictsprogressionofmetastaticmelanoma
AT quachchristine pd1blockadeontumormicroenvironmentresidentilc2spromotestnfaproductionandrestrictsprogressionofmetastaticmelanoma
AT painterjacobd pd1blockadeontumormicroenvironmentresidentilc2spromotestnfaproductionandrestrictsprogressionofmetastaticmelanoma
AT shafieijahanipedram pd1blockadeontumormicroenvironmentresidentilc2spromotestnfaproductionandrestrictsprogressionofmetastaticmelanoma
AT fungmarshall pd1blockadeontumormicroenvironmentresidentilc2spromotestnfaproductionandrestrictsprogressionofmetastaticmelanoma
AT gillparkashs pd1blockadeontumormicroenvironmentresidentilc2spromotestnfaproductionandrestrictsprogressionofmetastaticmelanoma
AT sorooshpejman pd1blockadeontumormicroenvironmentresidentilc2spromotestnfaproductionandrestrictsprogressionofmetastaticmelanoma
AT sharpearleneh pd1blockadeontumormicroenvironmentresidentilc2spromotestnfaproductionandrestrictsprogressionofmetastaticmelanoma
AT akbariomid pd1blockadeontumormicroenvironmentresidentilc2spromotestnfaproductionandrestrictsprogressionofmetastaticmelanoma