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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...

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Autores principales: Iwanowycz, Stephen, Ngoi, Soo, Li, Yingqi, Hill, Megan, Koivisto, Christopher, Parrish, Melodie, Guo, Beichu, Li, Zihai, Liu, Bei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
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.
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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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