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Dendritic cell rehab: new strategies to unleash therapeutic immunity in ovarian cancer

  • Focussed Research Review
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA

    Chang-Suk Chae, Eli Teran-Cabanillas & Juan R. Cubillos-Ruiz

  2. Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA

    Chang-Suk Chae, Eli Teran-Cabanillas & Juan R. Cubillos-Ruiz

  3. School of Nutrition Sciences, Autonomous University of Sinaloa, Culiacán, SIN, Mexico

    Eli Teran-Cabanillas

Authors
  1. Chang-Suk Chae
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Corresponding author

Correspondence to Juan R. Cubillos-Ruiz.

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Conflict of interest

Juan R. Cubillos-Ruiz is co-founder and scientific advisor for Quentis Therapeutics, Inc. The other authors declare no conflict of interest.

Additional information

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

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