Abstract
Immune-based therapies that induce remarkable and durable responses against melanoma and lung cancer have unfortunately demonstrated limited success in ovarian cancer patients. This is likely due to the exceptional immunoregulatory nature of ovarian tumors, which employ numerous strategies to effectively suppress anti-tumor immunity. Here, we summarize a decade of research indicating that ovarian cancers possess an exquisite capacity to subvert the activity of host dendritic cells (DCs) as a key mechanism to impede the development and maintenance of protective T cell-based immune responses. Identifying, understanding, and disabling the precise mechanisms promoting DC dysfunction in ovarian cancer are, therefore, fundamental requirements for devising the next generation of successful immunotherapies against this devastating malignancy.
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Abbreviations
- 4-HNE:
-
4-Hydroxynonenal
- BMDC:
-
Bone marrow-derived DC
- CCL3:
-
Chemokine (C-C motif) ligand 3
- CCL5:
-
Chemokine (C-C motif) ligand 5
- CCR6:
-
Chemokine receptor 6
- cDC:
-
Conventional DCs
- CRISPR/Cas9:
-
Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9
- CTLA4:
-
Cytotoxic T-lymphocyte-associated antigen 4
- DC:
-
Dendritic cell
- ER:
-
Endoplasmic reticulum
- IFN:
-
Interferon
- IRE1α:
-
Inositol-requiring enzyme 1
- miRNA:
-
MicroRNA
- MyD88:
-
Myeloid differentiation primary response gene 88
- PD-1:
-
Programmed cell death protein 1
- PD-L1:
-
Programmed cell death protein ligand 1
- pDC:
-
Plasmacytoid dendritic cells
- PEI:
-
Polyethylenimine
- PGE2:
-
Prostaglandin E2
- PIGF-1:
-
Placenta growth factor
- ROS:
-
Reactive oxygen species
- SATB1:
-
Special AT-rich sequence-binding protein-1
- sgRNA:
-
Single-guide RNA
- siRNA:
-
Small-interfering RNA
- tDC:
-
Tumor-associated DC
- TGF-β:
-
Tumor growth factor -β
- Th1:
-
T helper 1
- TLR:
-
Toll-like receptor
- TNF:
-
Tumor necrosis factor
- VEGF-A:
-
Vascular Endothelial Growth Factor-A
- XBP1:
-
X-box-binding protein 1
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Acknowledgements
Our research has been supported by the John H. Copenhaver, Jr. and William H. Thomas, MD 1952 Fellowship of the Geisel School of Medicine at Dartmouth (Juan R. Cubillos-Ruiz), the Irvington Institute Fellowship Program of the Cancer Research Institute (Juan R. Cubillos-Ruiz), the Ann Schreiber Mentored Investigator Award of the Ovarian Cancer Research Fund Alliance (Juan R. Cubillos-Ruiz), and the Ovarian Cancer Academy—Early Career Investigator Award of the Department of Defense (Juan R. Cubillos-Ruiz). We apologize to colleagues whose work was not cited in this review due to space limitations.
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Juan R. Cubillos-Ruiz is co-founder and scientific advisor for Quentis Therapeutics, Inc. The other authors declare no conflict of interest.
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This paper is a Focussed Research Review based on a presentation given at the conference Regulatory Myeloid Suppressor Cells: From Basic Discovery to Therapeutic Application which was hosted by the Wistar Institute in Philadelphia, PA, USA, 16th–19th June, 2016. It is part of a Cancer Immunology, Immunotherapy series of Focussed Research Reviews.
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Chae, CS., Teran-Cabanillas, E. & Cubillos-Ruiz, J.R. Dendritic cell rehab: new strategies to unleash therapeutic immunity in ovarian cancer. Cancer Immunol Immunother 66, 969–977 (2017). https://doi.org/10.1007/s00262-017-1958-2
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DOI: https://doi.org/10.1007/s00262-017-1958-2