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Front. Immunol. | doi: 10.3389/fimmu.2018.02759

Combination Strategies to Optimize Efficacy of Dendritic Cell-based Immunotherapy

 Mandy Van Gulijk1, Floris Dammeijer1, Joachim Aerts1 and  Heleen Vroman1*
  • 1Erasmus Medical Center, Erasmus University Rotterdam, Netherlands

Dendritic cells (DCs) are antigen-presenting cells (APCs) that are essential for the activation of immune responses. In various malignancies, these immunostimulatory properties are exploited by DC-therapy, aiming at the induction of effective anti-tumor immunity by vaccination with ex vivo antigen-loaded DCs. Depending on the type of DC-therapy used, long-term clinical efficacy upon DC-therapy remains restricted to a proportion of patients, likely due to lack of immunogenicity of tumor cells, presence of a stromal compartment, and the suppressive tumor microenvironment (TME) leading to the development of resistance. The efficacy of different types of DC-therapy is dependent on the type of DC used and which type of antigen is used. In order to circumvent tumor-induced suppressive mechanisms and unleash the full potential of DC-therapy, considerable efforts have been made to combine DC-therapy with chemotherapy, radiotherapy or with immunomodulatory therapeutics, such as checkpoint inhibitors. These combination strategies could enhance tumor immunogenicity, stimulate endogenous DCs following immunogenic cell death, improve infiltration of cytotoxic T lymphocytes (CTLs) or specifically deplete immunosuppressive cells in the TME, such as regulatory T-cells and myeloid-derived suppressor cells. In this review, different strategies of combining DC-therapy with immunomodulatory treatments will be discussed. These strategies and insights will improve and guide DC-based combination immunotherapies with the aim of further improving patient prognosis and care.

Keywords: DC-therapy, combination therapy, chemotherapy, Radiotherapy, immune check point inhibitors

Received: 31 Aug 2018; Accepted: 09 Nov 2018.

Edited by:

Patrik Andersson, Massachusetts General Hospital, Harvard Medical School, United States

Reviewed by:

Chandan Guha, Albert Einstein College of Medicine, United States
David Escors, University College London, United Kingdom  

Copyright: © 2018 Van Gulijk, Dammeijer, Aerts and Vroman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Heleen Vroman, Erasmus Medical Center, Erasmus University Rotterdam, Rotterdam, Netherlands, h.vroman@erasmusmc.nl