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), thereby leading to the development of resistance. 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 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.

Additional Metadata
Keywords chemotherapy, combination therapy, DC-therapy, immune checkpoint inhibitors, radiotherapy
Persistent URL dx.doi.org/10.3389/fimmu.2018.02759, hdl.handle.net/1765/113492
Journal Frontiers in Immunology
Citation
van Gulijk, M. (Mandy), Dammeijer, F, Aerts, J.G.J.V, & Vroman, H. (2018). Combination Strategies to Optimize Efficacy of Dendritic Cell-Based Immunotherapy. Frontiers in Immunology (Vol. 9). doi:10.3389/fimmu.2018.02759