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Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors
Type 2 DCs (DC2s) comprise the majority of conventional DCs within most tumors; however, little is known about their ability to initiate and sustain antitumor immunity, as most studies have focused on antigen cross-presenting DC1s. Here, we report that DC2 infiltration identified by analysis of mult...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492342/ https://www.ncbi.nlm.nih.gov/pubmed/34283809 http://dx.doi.org/10.1172/jci.insight.145885 |
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author | Iwanowycz, Stephen Ngoi, Soo Li, Yingqi Hill, Megan Koivisto, Christopher Parrish, Melodie Guo, Beichu Li, Zihai Liu, Bei |
author_facet | Iwanowycz, Stephen Ngoi, Soo Li, Yingqi Hill, Megan Koivisto, Christopher Parrish, Melodie Guo, Beichu Li, Zihai Liu, Bei |
author_sort | Iwanowycz, Stephen |
collection | PubMed |
description | Type 2 DCs (DC2s) comprise the majority of conventional DCs within most tumors; however, little is known about their ability to initiate and sustain antitumor immunity, as most studies have focused on antigen cross-presenting DC1s. Here, we report that DC2 infiltration identified by analysis of multiple human cancer data sets showed a significant correlation with survival across multiple human cancers, with the benefit being seen in tumors resistant to cytotoxic T cell control. Characterization of DC subtype infiltration into an immunotherapy-resistant model of breast cancer revealed that impairment of DC1s through 2 unique models resulted in enhanced DC2 functionality and improved tumor control. BATF3 deficiency depleted intratumoral DC1s, which led to increased DC2 lymph node migration and CD4(+) T cell activation. Enhancing DC2 stimulatory potential by genetic deletion of Hsp90b1 (encoding molecular chaperon GP96) led to a similar enhancement of T cell immunity and improved survival in a spontaneous breast cancer model. These data highlight the therapeutic and prognostic potential of DC2s within checkpoint blockade–resistant tumors. |
format | Online Article Text |
id | pubmed-8492342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-84923422021-10-07 Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors Iwanowycz, Stephen Ngoi, Soo Li, Yingqi Hill, Megan Koivisto, Christopher Parrish, Melodie Guo, Beichu Li, Zihai Liu, Bei JCI Insight Research Article Type 2 DCs (DC2s) comprise the majority of conventional DCs within most tumors; however, little is known about their ability to initiate and sustain antitumor immunity, as most studies have focused on antigen cross-presenting DC1s. Here, we report that DC2 infiltration identified by analysis of multiple human cancer data sets showed a significant correlation with survival across multiple human cancers, with the benefit being seen in tumors resistant to cytotoxic T cell control. Characterization of DC subtype infiltration into an immunotherapy-resistant model of breast cancer revealed that impairment of DC1s through 2 unique models resulted in enhanced DC2 functionality and improved tumor control. BATF3 deficiency depleted intratumoral DC1s, which led to increased DC2 lymph node migration and CD4(+) T cell activation. Enhancing DC2 stimulatory potential by genetic deletion of Hsp90b1 (encoding molecular chaperon GP96) led to a similar enhancement of T cell immunity and improved survival in a spontaneous breast cancer model. These data highlight the therapeutic and prognostic potential of DC2s within checkpoint blockade–resistant tumors. American Society for Clinical Investigation 2021-09-08 /pmc/articles/PMC8492342/ /pubmed/34283809 http://dx.doi.org/10.1172/jci.insight.145885 Text en © 2021 Iwanowycz et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Iwanowycz, Stephen Ngoi, Soo Li, Yingqi Hill, Megan Koivisto, Christopher Parrish, Melodie Guo, Beichu Li, Zihai Liu, Bei Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors |
title | Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors |
title_full | Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors |
title_fullStr | Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors |
title_full_unstemmed | Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors |
title_short | Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors |
title_sort | type 2 dendritic cells mediate control of cytotoxic t cell resistant tumors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492342/ https://www.ncbi.nlm.nih.gov/pubmed/34283809 http://dx.doi.org/10.1172/jci.insight.145885 |
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