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.
N1 - Publisher Copyright:
© 2015 by The American Association of Immunologists, Inc.
PY - 2015/7/1
Y1 - 2015/7/1
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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U2 - 10.4049/jimmunol.1401607
DO - 10.4049/jimmunol.1401607
M3 - Article
C2 - 26026061
AN - SCOPUS:84932170308
SN - 0022-1767
VL - 195
SP - 367
EP - 376
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -