Crosstalk between dendritic cell subsets and implications for dendritic cell-based anticancer immunotherapy

Abstract

Dendritic cells (DCs) are a family of professional antigen-presenting cells that have an indispensable role in the initiation of innate and adaptive immune responses against pathogens and tumor cells. The DC family is very heterogeneous. Two main types of naturally occurring DCs circulate in peripheral blood, each with its unique phenotypic and functional characteristics: myeloid DCs and plasmacytoid. There is an ample number of studies that have focused on the bi-directional crosstalk between DCs and natural killer cells or T cells. However, the crosstalk among the different DC subsets, in the context of infectious diseases and cancer, has until now not received much attention. Here, we review all available literature that has dealt with the crosstalk between plasmacytoid and myeloid DCs and the potential mode of action. Emphasis will be given to the therapeutic potential of the combination of DC subsets for DC-based immunotherapy.

Effective Clinical Responses in Metastatic Melanoma Patients after Vaccination with Primary Myeloid Dendritic Cells

“…MDCs and pDCs may utilize different mechanism and could synergize in the induction of clinical responses in metastatic melanoma patients. We therefore hypothesize that coadministration of naturally circulating mDCs and pDCs, and thus activation of multiple, possibly complementary, antitumor mechanisms, may generate more potent and longer-lasting antitumor responses in cancer patients compared with administration of individual naturally circulating DC subsets (17,40). Indeed, in a murine tumor model, simultaneous injection of mDCs and pDCs proved superior in generating antitumor responses when compared with immunization with either DC subset alone (41).…”

“…Although the trial was designed as a safety and feasibility study, we obtained promising clinical results; 7 of 15 metastatic melanoma patients were still alive two years after the initiation of treatment (14). Both activated pDCs, which produce high amounts of IFNa, and activated mDCs have the capacity to induce T helper 1 cells, cytotoxic T cells, natural killer cells, and natural killer T cells, leading to a potent cellular immune response (15)(16)(17). Moreover, primary mDCs isolated from healthy donors and cancer patients are able to prime tumor-specific CD8 þ T cells in vitro (18).…”

Dendritic cell vaccination in melanoma patients: From promising results to future perspectives

“…Co-culture of mDCs and pDCs during activation augments the expression of co-stimulatory molecules and secretion of proinflammatory cytokines, providing the rationale for combining mDCs and pDCs in a DC vaccine. 44 In a murine tumor model, immunization with a mixture of activated pDC and mDC resulted in increased levels of antigenspecific CD8…”

PLGA-Encapsulated Perfluorocarbon Nanoparticles for Simultaneous Visualization of Distinct Cell Populations by 19 F MRI

“…MRI has previously been used to monitor dendritic cell (DC) vaccines in melanoma patients using iron oxide contrast agents [3]. 19 F MRI is a relatively new imaging technique to be applied to cell tracking, and has several added advantages, chiefly, that it yields very specific images that allow for quantification of cell numbers without the use of radioactivity [4]. Nevertheless, a major problem with 19 F MRI for cell tracking has been the lack of stable, clinically applicable labels.…”

“…19 F MRI is a relatively new imaging technique to be applied to cell tracking, and has several added advantages, chiefly, that it yields very specific images that allow for quantification of cell numbers without the use of radioactivity [4]. Nevertheless, a major problem with 19 F MRI for cell tracking has been the lack of stable, clinically applicable labels. The fluorous agents responsible for the detected signal -most often perfluorocarbons (PFCs) -are not miscible with hydrophilic or hydrophobic solvents, and thus can be difficult to stabilize in a form suitable for cell uptake [5].…”