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CCL4 Secretion By Interleukin-15 Dendritic Cells Directs Superior Recruitment Of Cd56+ Cytolytic Lymphocytes

ABSTRACT: A key requisite for the success of a dendritic cell (DC)-based vaccine in treating malignancies is the capacity of the DCs to attract immune effector cells for further interaction and activation, considering crosstalk with DCs is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC therapy. In this paper we examine if the so-called interleukin (IL)-15 DC vaccine provides a favorable chemokine milieu for recruiting T cells, natural killer (NK) cells and gamma delta (γδ) T cells, in comparison with the IL-4 DCs used routinely for clinical studies, as well as the underlying mechanisms of immune cell attraction by IL-15 DCs. Chemokine signaling is studied both at the RNA level, using microarray data of mature DCs, and functional level, by means of a transwell chemotaxis assay. Important to note, the classic IL-4 DC vaccine falls short to attract the required immune effector lymphocytes, whereas the IL-15 DCs provide a favorable chemokine milieu for recruiting all cytolytic effector cells. The elevated secretion of the chemokine (C-C motif) ligand 4 (CCL4), also known as macrophage inflammatory protein-1β (MIP-1β), by IL-15 DCs underlies the enhanced migratory responsiveness of T cells, NK cells and γδ T cells. Namely, neutralizing its receptor CCR5 resulted in a significant drop in migration of the aforementioned effector cells towards IL-15 DCs. These findings should be kept in mind in the design of future DC-based cancer vaccines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE79184 | GEO | 2016/03/17

SECONDARY ACCESSION(S): PRJNA315119

REPOSITORIES: GEO

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