Functional and Phenotypic Analysis of Two-Day Monocyte-Derived Dendritic Cells Suitable for Immunotherapy Purposes

Background: Optimize the generation of clinical-grade monocyte-derived dendritic cells (DC) suitable for cancer immunotherapy affordable to cancer patients worldwide remains a formidable challenge.Although vaccination with DC pulsed with tumor-associated antigens (TAA) has been thoroughly evaluated in Caucasian individuals, the immunogenicity of DCs in Colombian individuals is yet to be explored.Methodology: Mononuclear cells obtained from buffy coats of healthy Colombian volunteers were used to compare the phenotype and proficiency as Antigen Presenting Cells (APC) of matured DCs obtained in two vs. seven days from monocytes purified either by adherence to plastic or by negative selection used fresh or after cryopreservation.Furthermore, the functional capacity of two types of 2d-DCs maturated with two different cytokine-cocktails: Standard (2d-stDCs) or Type I Alpha (2d-aDCs), to prime or boost TAA specific CD8+ T cells and to stimulate Th1 stem cells and follicular T helper CD4+ T-cells (TFH), was examined.Results: Both 2d-stDCs and 2d-aDCs exhibited a maturation profile similar to standard DCs obtained in seven days.Despite both types of DCs were efficient in stimulating antigen specific CD4+ and CD8+ T cells, only 2d-aDCs secreted high amounts of IL-12p70 and fostered more efficiently than 2d-stDCs the expansion of stem memory Th1, TFH cells and effector TAA specific CD8+ T cells.Conclusions: Two-day derived DCs are phenotypically and functionally equivalent to seven day derived DCs and are suitable for cancer immunotherapy in Colombian individuals.