Lenalidomide and Programmed Death-1 Blockade Synergistically Enhances the Effects of Dendritic Cell Vaccination in a Model of Murine Myeloma
The therapeutic efficacy of dendritic cell (DC)-based immunotherapy may be potentiated in combination with other anticancer therapies that enhance DC function by modulating immune responses and the tumor microenvironment. In this study, we investigated the efficacy of DC vaccination in combination w...
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doaj-337d0ecead764428bebbaa3062bff9fa2020-11-24T21:29:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-06-01910.3389/fimmu.2018.01370377570Lenalidomide and Programmed Death-1 Blockade Synergistically Enhances the Effects of Dendritic Cell Vaccination in a Model of Murine MyelomaManh-Cuong Vo0Manh-Cuong Vo1Sung-Hoon Jung2Sung-Hoon Jung3Tan-Huy Chu4Hyun-Ju Lee5Thangaraj Jaya Lakshmi6Hye-Seong Park7Hyeoung-Joon Kim8Joon Haeng Rhee9Joon Haeng Rhee10Je-Jung Lee11Je-Jung Lee12Je-Jung Lee13Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, South KoreaDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun, South KoreaResearch Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, South KoreaDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun, South KoreaResearch Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, South KoreaResearch Institute, VaxCell-Bio Therapeutics, Hwasun, South KoreaResearch Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, South KoreaResearch Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, South KoreaDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun, South KoreaResearch Institute, VaxCell-Bio Therapeutics, Hwasun, South KoreaDepartment of Microbiology and Clinical Vaccine R&D Center, Chonnam National University Medical School, Hwasun, South KoreaResearch Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, South KoreaDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun, South KoreaResearch Institute, VaxCell-Bio Therapeutics, Hwasun, South KoreaThe therapeutic efficacy of dendritic cell (DC)-based immunotherapy may be potentiated in combination with other anticancer therapies that enhance DC function by modulating immune responses and the tumor microenvironment. In this study, we investigated the efficacy of DC vaccination in combination with lenalidomide and programmed death (PD)-1 blockade in a model of murine myeloma. MOPC-315 cell lines were injected subcutaneously to establish myeloma-bearing mice and the following five test groups were established: PBS control, DCs, DCs + lenalidomide, DCs + PD-1 blockade, and DCs + lenalidomide + PD-1 blockade. The combination of DCs plus lenalidomide and PD-1 blockade more potently inhibited tumor growth compared to the other groups. This effect was associated with a reduction in immune suppressor cells (such as myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells) and an increase in immune effector cells [such as CD4+ and CD8+ T cells, natural killer (NK) cells, and M1 macrophages] in the spleen. Functional activities of cytotoxic T lymphocytes and NK cells were also enhanced by the triple combination. Levels of immunosuppressive cytokines, such as TGF-β and IL-10, were significantly reduced in the tumor microenvironment. These findings suggest that the combination of DCs plus lenalidomide and PD-1 blockade synergistically establishes a robust anti-myeloma immunity through a two-way mechanism, which inhibits immunosuppressive cells while activating effector cells with superior polarization of the Th1/Th2 balance in favor of the tumor immune response. This result should provide an experimental ground for incorporating check point inhibitors to existing immunotherapeutic modalities against multiple myeloma.https://www.frontiersin.org/article/10.3389/fimmu.2018.01370/fullmyelomadendritic cellslenaldiomideanti-PD-1cancer immunotherapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Manh-Cuong Vo Manh-Cuong Vo Sung-Hoon Jung Sung-Hoon Jung Tan-Huy Chu Hyun-Ju Lee Thangaraj Jaya Lakshmi Hye-Seong Park Hyeoung-Joon Kim Joon Haeng Rhee Joon Haeng Rhee Je-Jung Lee Je-Jung Lee Je-Jung Lee |
spellingShingle |
Manh-Cuong Vo Manh-Cuong Vo Sung-Hoon Jung Sung-Hoon Jung Tan-Huy Chu Hyun-Ju Lee Thangaraj Jaya Lakshmi Hye-Seong Park Hyeoung-Joon Kim Joon Haeng Rhee Joon Haeng Rhee Je-Jung Lee Je-Jung Lee Je-Jung Lee Lenalidomide and Programmed Death-1 Blockade Synergistically Enhances the Effects of Dendritic Cell Vaccination in a Model of Murine Myeloma Frontiers in Immunology myeloma dendritic cells lenaldiomide anti-PD-1 cancer immunotherapy |
author_facet |
Manh-Cuong Vo Manh-Cuong Vo Sung-Hoon Jung Sung-Hoon Jung Tan-Huy Chu Hyun-Ju Lee Thangaraj Jaya Lakshmi Hye-Seong Park Hyeoung-Joon Kim Joon Haeng Rhee Joon Haeng Rhee Je-Jung Lee Je-Jung Lee Je-Jung Lee |
author_sort |
Manh-Cuong Vo |
title |
Lenalidomide and Programmed Death-1 Blockade Synergistically Enhances the Effects of Dendritic Cell Vaccination in a Model of Murine Myeloma |
title_short |
Lenalidomide and Programmed Death-1 Blockade Synergistically Enhances the Effects of Dendritic Cell Vaccination in a Model of Murine Myeloma |
title_full |
Lenalidomide and Programmed Death-1 Blockade Synergistically Enhances the Effects of Dendritic Cell Vaccination in a Model of Murine Myeloma |
title_fullStr |
Lenalidomide and Programmed Death-1 Blockade Synergistically Enhances the Effects of Dendritic Cell Vaccination in a Model of Murine Myeloma |
title_full_unstemmed |
Lenalidomide and Programmed Death-1 Blockade Synergistically Enhances the Effects of Dendritic Cell Vaccination in a Model of Murine Myeloma |
title_sort |
lenalidomide and programmed death-1 blockade synergistically enhances the effects of dendritic cell vaccination in a model of murine myeloma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-06-01 |
description |
The therapeutic efficacy of dendritic cell (DC)-based immunotherapy may be potentiated in combination with other anticancer therapies that enhance DC function by modulating immune responses and the tumor microenvironment. In this study, we investigated the efficacy of DC vaccination in combination with lenalidomide and programmed death (PD)-1 blockade in a model of murine myeloma. MOPC-315 cell lines were injected subcutaneously to establish myeloma-bearing mice and the following five test groups were established: PBS control, DCs, DCs + lenalidomide, DCs + PD-1 blockade, and DCs + lenalidomide + PD-1 blockade. The combination of DCs plus lenalidomide and PD-1 blockade more potently inhibited tumor growth compared to the other groups. This effect was associated with a reduction in immune suppressor cells (such as myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells) and an increase in immune effector cells [such as CD4+ and CD8+ T cells, natural killer (NK) cells, and M1 macrophages] in the spleen. Functional activities of cytotoxic T lymphocytes and NK cells were also enhanced by the triple combination. Levels of immunosuppressive cytokines, such as TGF-β and IL-10, were significantly reduced in the tumor microenvironment. These findings suggest that the combination of DCs plus lenalidomide and PD-1 blockade synergistically establishes a robust anti-myeloma immunity through a two-way mechanism, which inhibits immunosuppressive cells while activating effector cells with superior polarization of the Th1/Th2 balance in favor of the tumor immune response. This result should provide an experimental ground for incorporating check point inhibitors to existing immunotherapeutic modalities against multiple myeloma. |
topic |
myeloma dendritic cells lenaldiomide anti-PD-1 cancer immunotherapy |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.01370/full |
work_keys_str_mv |
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