Dendritic cell-based vaccines that utilize myeloid rather than plasmacytoid cells offer a superior survival advantage in malignant glioma

Mahua Dey, Alan L. Chang, Jason Miska, Derek A. Wainwright, Atique U. Ahmed, Irina V. Balyasnikova, Peter Pytel, Yu Han, Alex Tobias, Lingjiao Zhang, Jian Qiao, Maciej S. Lesniak*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Dendritic cells (DCs) are professional APCs that are traditionally divided into two distinct subsets, myeloid DC (mDCs) and plasmacytoid DC (pDCs). pDCs are known for their ability to secrete large amounts of IFN-a. Apart from IFN-a production, pDCs can also process Ag and induce T cell immunity or tolerance. In several solid tumors, pDCs have been shown to play a critical role in promoting tumor immunosuppression. We investigated the role of pDCs in the process of glioma progression in the syngeneic murine model of glioma. We show that glioma-infiltrating pDCs are the major APC in glioma and are deficient in IFN-a secretion (p < 0.05). pDC depletion leads to increased survival of the mice bearing intracranial tumor by decreasing the number of regulatory T cells (Tregs) and by decreasing the suppressive capabilities of Tregs. We subsequently compared the ability of mDCs and pDCs to generate effective antiglioma immunity in a GL261-OVA mouse model of glioma. Our data suggest that mature pDCs and mDCs isolated from naive mice can be effectively activated and loaded with SIINFEKL Ag in vitro. Upon intradermal injection in the hindleg, a fraction of both types of DCs migrate to the brain and lymph nodes. Compared to mice vaccinated with pDC or control mice, mice vaccinated with mDCs generate a robust Th1 type immune response, characterized by high frequency of CD4+T-bet+ T cells and CD8+SIINFEKEL+ T cells. This robust antitumor T cell response results in tumor eradication and longterm survival in 60% of the animals (p < 0.001).

Original languageEnglish (US)
Pages (from-to)367-376
Number of pages10
JournalJournal of Immunology
Volume195
Issue number1
DOIs
StatePublished - Jul 1 2015

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Glioma
Dendritic Cells
Vaccines
T-Lymphocytes
Immunity
Neoplasms
Intradermal Injections
Regulatory T-Lymphocytes
Myeloid Cells
Immunosuppression
Lymph Nodes
Brain

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "Dendritic cell-based vaccines that utilize myeloid rather than plasmacytoid cells offer a superior survival advantage in malignant glioma",
abstract = "Dendritic cells (DCs) are professional APCs that are traditionally divided into two distinct subsets, myeloid DC (mDCs) and plasmacytoid DC (pDCs). pDCs are known for their ability to secrete large amounts of IFN-a. Apart from IFN-a production, pDCs can also process Ag and induce T cell immunity or tolerance. In several solid tumors, pDCs have been shown to play a critical role in promoting tumor immunosuppression. We investigated the role of pDCs in the process of glioma progression in the syngeneic murine model of glioma. We show that glioma-infiltrating pDCs are the major APC in glioma and are deficient in IFN-a secretion (p < 0.05). pDC depletion leads to increased survival of the mice bearing intracranial tumor by decreasing the number of regulatory T cells (Tregs) and by decreasing the suppressive capabilities of Tregs. We subsequently compared the ability of mDCs and pDCs to generate effective antiglioma immunity in a GL261-OVA mouse model of glioma. Our data suggest that mature pDCs and mDCs isolated from naive mice can be effectively activated and loaded with SIINFEKL Ag in vitro. Upon intradermal injection in the hindleg, a fraction of both types of DCs migrate to the brain and lymph nodes. Compared to mice vaccinated with pDC or control mice, mice vaccinated with mDCs generate a robust Th1 type immune response, characterized by high frequency of CD4+T-bet+ T cells and CD8+SIINFEKEL+ T cells. This robust antitumor T cell response results in tumor eradication and longterm survival in 60{\%} of the animals (p < 0.001).",
author = "Mahua Dey and Chang, {Alan L.} and Jason Miska and Wainwright, {Derek A.} and Ahmed, {Atique U.} and Balyasnikova, {Irina V.} and Peter Pytel and Yu Han and Alex Tobias and Lingjiao Zhang and Jian Qiao and Lesniak, {Maciej S.}",
year = "2015",
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Dendritic cell-based vaccines that utilize myeloid rather than plasmacytoid cells offer a superior survival advantage in malignant glioma. / Dey, Mahua; Chang, Alan L.; Miska, Jason; Wainwright, Derek A.; Ahmed, Atique U.; Balyasnikova, Irina V.; Pytel, Peter; Han, Yu; Tobias, Alex; Zhang, Lingjiao; Qiao, Jian; Lesniak, Maciej S.

In: Journal of Immunology, Vol. 195, No. 1, 01.07.2015, p. 367-376.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dendritic cell-based vaccines that utilize myeloid rather than plasmacytoid cells offer a superior survival advantage in malignant glioma

AU - Dey, Mahua

AU - Chang, Alan L.

AU - Miska, Jason

AU - Wainwright, Derek A.

AU - Ahmed, Atique U.

AU - Balyasnikova, Irina V.

AU - Pytel, Peter

AU - Han, Yu

AU - Tobias, Alex

AU - Zhang, Lingjiao

AU - Qiao, Jian

AU - Lesniak, Maciej S.

PY - 2015/7/1

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N2 - Dendritic cells (DCs) are professional APCs that are traditionally divided into two distinct subsets, myeloid DC (mDCs) and plasmacytoid DC (pDCs). pDCs are known for their ability to secrete large amounts of IFN-a. Apart from IFN-a production, pDCs can also process Ag and induce T cell immunity or tolerance. In several solid tumors, pDCs have been shown to play a critical role in promoting tumor immunosuppression. We investigated the role of pDCs in the process of glioma progression in the syngeneic murine model of glioma. We show that glioma-infiltrating pDCs are the major APC in glioma and are deficient in IFN-a secretion (p < 0.05). pDC depletion leads to increased survival of the mice bearing intracranial tumor by decreasing the number of regulatory T cells (Tregs) and by decreasing the suppressive capabilities of Tregs. We subsequently compared the ability of mDCs and pDCs to generate effective antiglioma immunity in a GL261-OVA mouse model of glioma. Our data suggest that mature pDCs and mDCs isolated from naive mice can be effectively activated and loaded with SIINFEKL Ag in vitro. Upon intradermal injection in the hindleg, a fraction of both types of DCs migrate to the brain and lymph nodes. Compared to mice vaccinated with pDC or control mice, mice vaccinated with mDCs generate a robust Th1 type immune response, characterized by high frequency of CD4+T-bet+ T cells and CD8+SIINFEKEL+ T cells. This robust antitumor T cell response results in tumor eradication and longterm survival in 60% of the animals (p < 0.001).

AB - Dendritic cells (DCs) are professional APCs that are traditionally divided into two distinct subsets, myeloid DC (mDCs) and plasmacytoid DC (pDCs). pDCs are known for their ability to secrete large amounts of IFN-a. Apart from IFN-a production, pDCs can also process Ag and induce T cell immunity or tolerance. In several solid tumors, pDCs have been shown to play a critical role in promoting tumor immunosuppression. We investigated the role of pDCs in the process of glioma progression in the syngeneic murine model of glioma. We show that glioma-infiltrating pDCs are the major APC in glioma and are deficient in IFN-a secretion (p < 0.05). pDC depletion leads to increased survival of the mice bearing intracranial tumor by decreasing the number of regulatory T cells (Tregs) and by decreasing the suppressive capabilities of Tregs. We subsequently compared the ability of mDCs and pDCs to generate effective antiglioma immunity in a GL261-OVA mouse model of glioma. Our data suggest that mature pDCs and mDCs isolated from naive mice can be effectively activated and loaded with SIINFEKL Ag in vitro. Upon intradermal injection in the hindleg, a fraction of both types of DCs migrate to the brain and lymph nodes. Compared to mice vaccinated with pDC or control mice, mice vaccinated with mDCs generate a robust Th1 type immune response, characterized by high frequency of CD4+T-bet+ T cells and CD8+SIINFEKEL+ T cells. This robust antitumor T cell response results in tumor eradication and longterm survival in 60% of the animals (p < 0.001).

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