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HDAC9 deficiency promotes tumor progression by decreasing the CD8(+) dendritic cell infiltration of the tumor microenvironment

BACKGROUND: The tumor microenvironment (TME) contains a variety of immune cells, which play critical roles during the multistep development of tumors. Histone deacetylase 9 (HDAC9) has been reported to have either proinflammatory or anti-inflammatory effects, depending on the immune environment. In...

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Autores principales: Ning, Yongling, Ding, Jun, Sun, Xiao, Xie, Yewen, Su, Mingming, Ma, Chenglong, Pan, Jie, Chen, Jie, Jiang, Hua, Qi, Chunjian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304847/
https://www.ncbi.nlm.nih.gov/pubmed/32554611
http://dx.doi.org/10.1136/jitc-2020-000529
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author Ning, Yongling
Ding, Jun
Sun, Xiao
Xie, Yewen
Su, Mingming
Ma, Chenglong
Pan, Jie
Chen, Jie
Jiang, Hua
Qi, Chunjian
author_facet Ning, Yongling
Ding, Jun
Sun, Xiao
Xie, Yewen
Su, Mingming
Ma, Chenglong
Pan, Jie
Chen, Jie
Jiang, Hua
Qi, Chunjian
author_sort Ning, Yongling
collection PubMed
description BACKGROUND: The tumor microenvironment (TME) contains a variety of immune cells, which play critical roles during the multistep development of tumors. Histone deacetylase 9 (HDAC9) has been reported to have either proinflammatory or anti-inflammatory effects, depending on the immune environment. In this study, we investigated whether HDAC9 in the tumor stroma regulated inflammation and antitumor immunity. METHODS: Hdac9 knockout mice were generated to analyze the HDAC9-associated inflammation and tumor progression. Immune cells and cytokines in TME or draining lymph nodes were quantified by flow cytometry and quantitative reverse transcription-PCR. The antigen presentation and CD8(+) T cell priming by tumor-infiltrating dendritic cells (DCs) were evaluated in vitro and in vivo. HDAC9-associated inflammation was investigated in a mouse model with dextran sulfate sodium–induced colitis. Correlation of HDAC9 with CD8(+) expression was assessed in tissue sections from patients with non-small cell lung cancer. RESULTS: HDAC9 deficiency promoted tumor progression by decreasing the CD8(+) DC infiltration of the TME. Compared with wild-type mice, the tumor-infiltrating DCs of Hdac9(-/-) mice displayed impaired cross-presentation of tumor antigens and cross-priming of CD8(+) T cells. Moreover, HDAC9 expression was significantly positively correlated with CD8(+) cell counts in human lung cancer stroma samples. CONCLUSIONS: HDAC9 deficiency decreased inflammation and promoted tumor progression by decreasing CD8(+) DC infiltration of the TME. HDAC9 expression in the tumor stroma may represent a promising biomarker to predict the therapeutic responses of patients receiving CD8(+) T cell-dependent immune treatment regimens.
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spelling pubmed-73048472020-06-22 HDAC9 deficiency promotes tumor progression by decreasing the CD8(+) dendritic cell infiltration of the tumor microenvironment Ning, Yongling Ding, Jun Sun, Xiao Xie, Yewen Su, Mingming Ma, Chenglong Pan, Jie Chen, Jie Jiang, Hua Qi, Chunjian J Immunother Cancer Basic Tumor Immunology BACKGROUND: The tumor microenvironment (TME) contains a variety of immune cells, which play critical roles during the multistep development of tumors. Histone deacetylase 9 (HDAC9) has been reported to have either proinflammatory or anti-inflammatory effects, depending on the immune environment. In this study, we investigated whether HDAC9 in the tumor stroma regulated inflammation and antitumor immunity. METHODS: Hdac9 knockout mice were generated to analyze the HDAC9-associated inflammation and tumor progression. Immune cells and cytokines in TME or draining lymph nodes were quantified by flow cytometry and quantitative reverse transcription-PCR. The antigen presentation and CD8(+) T cell priming by tumor-infiltrating dendritic cells (DCs) were evaluated in vitro and in vivo. HDAC9-associated inflammation was investigated in a mouse model with dextran sulfate sodium–induced colitis. Correlation of HDAC9 with CD8(+) expression was assessed in tissue sections from patients with non-small cell lung cancer. RESULTS: HDAC9 deficiency promoted tumor progression by decreasing the CD8(+) DC infiltration of the TME. Compared with wild-type mice, the tumor-infiltrating DCs of Hdac9(-/-) mice displayed impaired cross-presentation of tumor antigens and cross-priming of CD8(+) T cells. Moreover, HDAC9 expression was significantly positively correlated with CD8(+) cell counts in human lung cancer stroma samples. CONCLUSIONS: HDAC9 deficiency decreased inflammation and promoted tumor progression by decreasing CD8(+) DC infiltration of the TME. HDAC9 expression in the tumor stroma may represent a promising biomarker to predict the therapeutic responses of patients receiving CD8(+) T cell-dependent immune treatment regimens. BMJ Publishing Group 2020-06-17 /pmc/articles/PMC7304847/ /pubmed/32554611 http://dx.doi.org/10.1136/jitc-2020-000529 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Basic Tumor Immunology
Ning, Yongling
Ding, Jun
Sun, Xiao
Xie, Yewen
Su, Mingming
Ma, Chenglong
Pan, Jie
Chen, Jie
Jiang, Hua
Qi, Chunjian
HDAC9 deficiency promotes tumor progression by decreasing the CD8(+) dendritic cell infiltration of the tumor microenvironment
title HDAC9 deficiency promotes tumor progression by decreasing the CD8(+) dendritic cell infiltration of the tumor microenvironment
title_full HDAC9 deficiency promotes tumor progression by decreasing the CD8(+) dendritic cell infiltration of the tumor microenvironment
title_fullStr HDAC9 deficiency promotes tumor progression by decreasing the CD8(+) dendritic cell infiltration of the tumor microenvironment
title_full_unstemmed HDAC9 deficiency promotes tumor progression by decreasing the CD8(+) dendritic cell infiltration of the tumor microenvironment
title_short HDAC9 deficiency promotes tumor progression by decreasing the CD8(+) dendritic cell infiltration of the tumor microenvironment
title_sort hdac9 deficiency promotes tumor progression by decreasing the cd8(+) dendritic cell infiltration of the tumor microenvironment
topic Basic Tumor Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304847/
https://www.ncbi.nlm.nih.gov/pubmed/32554611
http://dx.doi.org/10.1136/jitc-2020-000529
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