Monocyte-derived dendritic cells are essential for CD8+ T cell activation and anti-tumor responses after local immunotherapy
Tumors harbor several populations of dendritic cells with the ability to prime tumor-specific T cells. However, these T cells mostly fail to differentiate into armed effectors and are unable to control tumor growth. We have previously shown that treatment with immunostimulatory agents at the tumor s...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2015-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00584/full |
| _version_ | 1819264564129169408 |
|---|---|
| author | Sabine eKuhn Jianping eYang F eRonchese |
| author_facet | Sabine eKuhn Jianping eYang F eRonchese |
| author_sort | Sabine eKuhn |
| collection | DOAJ |
| description | Tumors harbor several populations of dendritic cells with the ability to prime tumor-specific T cells. However, these T cells mostly fail to differentiate into armed effectors and are unable to control tumor growth. We have previously shown that treatment with immunostimulatory agents at the tumor site can activate anti-tumor immune responses, and is associated with the appearance of a population of monocyte-derived dendritic cells in the tumor and tumor-draining lymph node. Here we use dendritic cell or monocyte depletion and monocyte transfer to show that these monocyte-derived dendritic cells are critical to the activation of anti-tumor immune responses. Treatment with the immunostimulatory agents Monosodium Urate crystals and Mycobacterium smegmatis induced the accumulation of monocytes in the draining lymph node, their upregulation of CD11c and MHCII, and expression of iNOS, TNFα and IL12p40. Blocking monocyte entry into the lymph node and tumor through neutralization of the chemokine CCL2 or inhibition of Colony Stimulating Factor-1 receptor signaling prevented the generation of monocyte-derived dendritic cells, the infiltration of tumor-specific T cells into the tumor, and anti-tumor responses. In a reciprocal fashion, monocytes transferred into mice depleted of CD11c+ cells were sufficient to rescue CD8+ T cell priming in lymph node and delay tumor growth. Thus monocytes exposed to the appropriate conditions become powerful activators of tumor-specific CD8+ T cells and anti-tumor immunity. |
| first_indexed | 2024-12-23T20:31:29Z |
| format | Article |
| id | doaj.art-8021a71c020f4e25841daa4a06643b0e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T20:31:29Z |
| publishDate | 2015-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8021a71c020f4e25841daa4a06643b0e2022-12-21T17:32:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-11-01610.3389/fimmu.2015.00584171611Monocyte-derived dendritic cells are essential for CD8+ T cell activation and anti-tumor responses after local immunotherapySabine eKuhn0Jianping eYang1F eRonchese2Malaghan Institute of Medical ResearchMalaghan Institute of Medical ResearchMalaghan Institute of Medical ResearchTumors harbor several populations of dendritic cells with the ability to prime tumor-specific T cells. However, these T cells mostly fail to differentiate into armed effectors and are unable to control tumor growth. We have previously shown that treatment with immunostimulatory agents at the tumor site can activate anti-tumor immune responses, and is associated with the appearance of a population of monocyte-derived dendritic cells in the tumor and tumor-draining lymph node. Here we use dendritic cell or monocyte depletion and monocyte transfer to show that these monocyte-derived dendritic cells are critical to the activation of anti-tumor immune responses. Treatment with the immunostimulatory agents Monosodium Urate crystals and Mycobacterium smegmatis induced the accumulation of monocytes in the draining lymph node, their upregulation of CD11c and MHCII, and expression of iNOS, TNFα and IL12p40. Blocking monocyte entry into the lymph node and tumor through neutralization of the chemokine CCL2 or inhibition of Colony Stimulating Factor-1 receptor signaling prevented the generation of monocyte-derived dendritic cells, the infiltration of tumor-specific T cells into the tumor, and anti-tumor responses. In a reciprocal fashion, monocytes transferred into mice depleted of CD11c+ cells were sufficient to rescue CD8+ T cell priming in lymph node and delay tumor growth. Thus monocytes exposed to the appropriate conditions become powerful activators of tumor-specific CD8+ T cells and anti-tumor immunity.http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00584/fullDendritic CellsT cellsmouse modelsTumor immunotherapyMonocyte-derived dendritic cellsCsf1r |
| spellingShingle | Sabine eKuhn Jianping eYang F eRonchese Monocyte-derived dendritic cells are essential for CD8+ T cell activation and anti-tumor responses after local immunotherapy Frontiers in Immunology Dendritic Cells T cells mouse models Tumor immunotherapy Monocyte-derived dendritic cells Csf1r |
| title | Monocyte-derived dendritic cells are essential for CD8+ T cell activation and anti-tumor responses after local immunotherapy |
| title_full | Monocyte-derived dendritic cells are essential for CD8+ T cell activation and anti-tumor responses after local immunotherapy |
| title_fullStr | Monocyte-derived dendritic cells are essential for CD8+ T cell activation and anti-tumor responses after local immunotherapy |
| title_full_unstemmed | Monocyte-derived dendritic cells are essential for CD8+ T cell activation and anti-tumor responses after local immunotherapy |
| title_short | Monocyte-derived dendritic cells are essential for CD8+ T cell activation and anti-tumor responses after local immunotherapy |
| title_sort | monocyte derived dendritic cells are essential for cd8 t cell activation and anti tumor responses after local immunotherapy |
| topic | Dendritic Cells T cells mouse models Tumor immunotherapy Monocyte-derived dendritic cells Csf1r |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00584/full |
| work_keys_str_mv | AT sabineekuhn monocytederiveddendriticcellsareessentialforcd8tcellactivationandantitumorresponsesafterlocalimmunotherapy AT jianpingeyang monocytederiveddendriticcellsareessentialforcd8tcellactivationandantitumorresponsesafterlocalimmunotherapy AT feronchese monocytederiveddendriticcellsareessentialforcd8tcellactivationandantitumorresponsesafterlocalimmunotherapy |