Clec9A + dendritic cells are not essential for antitumor CD8 + T cell responses induced by poly I:C immunotherapy
In the steady state, tumors harbor several populations of dendritic cells (DCs) and myeloid cells that are key regulators of the intratumoral immune environment. Among these cells, migratory CD103+ cross-presenting DCs are thought to be critical for tumor-specific CTL responses and tumor resistance....
Saved in:
Main Authors: | , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2019
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/82502 http://hdl.handle.net/10220/49073 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-82502 |
---|---|
record_format |
dspace |
spelling |
sg-ntu-dr.10356-825022020-03-07T12:18:05Z Clec9A + dendritic cells are not essential for antitumor CD8 + T cell responses induced by poly I:C immunotherapy Gilfillan, Connie B. Kuhn, Sabine Baey, Camille Hyde, Evelyn J. Yang, Jianping Ruedl, Christiane Ronchese, Franca School of Biological Sciences Science::Biological sciences Dendritic Cells CD8+ T Cell In the steady state, tumors harbor several populations of dendritic cells (DCs) and myeloid cells that are key regulators of the intratumoral immune environment. Among these cells, migratory CD103+ cross-presenting DCs are thought to be critical for tumor-specific CTL responses and tumor resistance. However, it is unclear whether this prominent role also extends to immunotherapy. We used a murine orthotopic mammary tumor model, as well as Clec9A–diphtheria toxin receptor mice that can be depleted of the specialized cross-presenting CD8α+ and CD103+ DC1 subsets, to investigate the role of these DCs in immunotherapy. Treatment with monosodium urate crystals and mycobacteria at the tumor site delayed tumor growth and required DC1s for efficacy. In contrast, treatment with poly I:C was equally effective regardless of DC1 depletion. Neither treatment affected myeloid-derived suppressor cell numbers in the spleen or tumor. Similar experiments using subcutaneous B16 melanoma tumors in BATF3-knockout mice confirmed that CD103+ DCs were not necessary for successful poly I:C immunotherapy. Nevertheless, adaptive immune responses were essential for the response to poly I:C, because mice depleted of CD8+ T cells or all DC subsets were unable to delay tumor growth. In vivo experiments showed that DC1 and DC2 subsets were able to take up tumor Ags, with DC2s making up the larger proportion of lymph node DCs carrying tumor material. Both DC subsets were able to cross-present OVA to OT-I T cells in vitro. Thus, immunotherapy with poly I:C enables multiple DC subsets to cross-present tumor Ag for effective antitumor immune responses. 2019-07-02T03:37:22Z 2019-12-06T14:56:53Z 2019-07-02T03:37:22Z 2019-12-06T14:56:53Z 2018 Journal Article Gilfillan, C. B., Kuhn, S., Baey, C., Hyde, E. J., Yang, J., Ruedl, C., & Ronchese, F. (2018). Clec9A + dendritic cells are not essential for antitumor CD8 + T cell responses induced by poly I:C immunotherapy. Journal of Immunology, 200(8), 2978-2986. doi:10.4049/jimmunol.1701593 0022-1767 https://hdl.handle.net/10356/82502 http://hdl.handle.net/10220/49073 10.4049/jimmunol.1701593 en Journal of Immunology © 2018 The American Association of Immunologists, Inc. All rights reserved. |
institution |
Nanyang Technological University |
building |
NTU Library |
country |
Singapore |
collection |
DR-NTU |
language |
English |
topic |
Science::Biological sciences Dendritic Cells CD8+ T Cell |
spellingShingle |
Science::Biological sciences Dendritic Cells CD8+ T Cell Gilfillan, Connie B. Kuhn, Sabine Baey, Camille Hyde, Evelyn J. Yang, Jianping Ruedl, Christiane Ronchese, Franca Clec9A + dendritic cells are not essential for antitumor CD8 + T cell responses induced by poly I:C immunotherapy |
description |
In the steady state, tumors harbor several populations of dendritic cells (DCs) and myeloid cells that are key regulators of the intratumoral immune environment. Among these cells, migratory CD103+ cross-presenting DCs are thought to be critical for tumor-specific CTL responses and tumor resistance. However, it is unclear whether this prominent role also extends to immunotherapy. We used a murine orthotopic mammary tumor model, as well as Clec9A–diphtheria toxin receptor mice that can be depleted of the specialized cross-presenting CD8α+ and CD103+ DC1 subsets, to investigate the role of these DCs in immunotherapy. Treatment with monosodium urate crystals and mycobacteria at the tumor site delayed tumor growth and required DC1s for efficacy. In contrast, treatment with poly I:C was equally effective regardless of DC1 depletion. Neither treatment affected myeloid-derived suppressor cell numbers in the spleen or tumor. Similar experiments using subcutaneous B16 melanoma tumors in BATF3-knockout mice confirmed that CD103+ DCs were not necessary for successful poly I:C immunotherapy. Nevertheless, adaptive immune responses were essential for the response to poly I:C, because mice depleted of CD8+ T cells or all DC subsets were unable to delay tumor growth. In vivo experiments showed that DC1 and DC2 subsets were able to take up tumor Ags, with DC2s making up the larger proportion of lymph node DCs carrying tumor material. Both DC subsets were able to cross-present OVA to OT-I T cells in vitro. Thus, immunotherapy with poly I:C enables multiple DC subsets to cross-present tumor Ag for effective antitumor immune responses. |
author2 |
School of Biological Sciences |
author_facet |
School of Biological Sciences Gilfillan, Connie B. Kuhn, Sabine Baey, Camille Hyde, Evelyn J. Yang, Jianping Ruedl, Christiane Ronchese, Franca |
format |
Article |
author |
Gilfillan, Connie B. Kuhn, Sabine Baey, Camille Hyde, Evelyn J. Yang, Jianping Ruedl, Christiane Ronchese, Franca |
author_sort |
Gilfillan, Connie B. |
title |
Clec9A + dendritic cells are not essential for antitumor CD8 + T cell responses induced by poly I:C immunotherapy |
title_short |
Clec9A + dendritic cells are not essential for antitumor CD8 + T cell responses induced by poly I:C immunotherapy |
title_full |
Clec9A + dendritic cells are not essential for antitumor CD8 + T cell responses induced by poly I:C immunotherapy |
title_fullStr |
Clec9A + dendritic cells are not essential for antitumor CD8 + T cell responses induced by poly I:C immunotherapy |
title_full_unstemmed |
Clec9A + dendritic cells are not essential for antitumor CD8 + T cell responses induced by poly I:C immunotherapy |
title_sort |
clec9a + dendritic cells are not essential for antitumor cd8 + t cell responses induced by poly i:c immunotherapy |
publishDate |
2019 |
url |
https://hdl.handle.net/10356/82502 http://hdl.handle.net/10220/49073 |
_version_ |
1681044633668288512 |