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Calcium ionophore pre-treatment induces type-1 polarized DCs with enhanced T cell stimulatory function and IL-12 production
  1. Erik Berk1,
  2. Shuwen Xu1,
  3. Min Xu1,
  4. Julia Terhune1 and
  5. Brian Czerniecki1,2
  1. Aff1 grid.25879.310000000419368972Department of Surgery and the Harrison Surgical Research CenterUniversity of Pennsylvania Philadelphia PA USA
  2. Aff2 grid.25879.310000000419368972Rena Rowan Breast Cancer CenterUniversity of Pennsylvania Philadelphia PA USA

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Meeting abstracts

The effective treatment of cancer by immunotherapy requires the induction of high numbers of tumor-specific type-1 polarized T cells. Since DCs are the key antigen-presenting cells capable of activating and polarizing T cells, the generation of type-1 polarized DCs for DC-based anti-cancer therapies is desired. We have previously shown that DCs matured with calcium ionophore (CI) alone results in the generation of type-2 polarized DCs, which lack IL-12 production. However, we now show that pre-treatment of monocyte-derived DCs with CI followed by the maturation with the inflammatory cytokine IFNγ and the TLR agonists LPS (TLR2) and R848 (TLR7/8), results in an enhanced IL-12 production by the DCs compared to DCs matured without CI pre-treatment. The effect of CI on IL-12 production appears to be dependent on the kinetics of CI pre-treatment as well as on the maturation factors used following CI addition. The CI-matured DCs show a more mature phenotype (based on CD83 and CCR7 expression), express higher levels of the co-stimulatory molecule CD70, and have reduced expression of the inhibitory molecule PD-L1 compared to DCs matured without CI-pre-treatment. When loaded with antigen these CI-matured DCs strongly induce T cell proliferation and the expression of the cytolytic proteins granzyme B and perforin by CD8+ T cells in a mixed leukocyte reaction. The ability of CI to induce type-1 polarization with enhanced IL-12 secretion and T cell stimulatory function allows for the development of type-1 polarized DC-based anti-cancer vaccines.