High Functional CD70 Expression on α‐Type 1‐Polarized Dendritic Cells from Patients with Chronic Lymphocytic Leukaemia

Abstract

Antigen-loaded dendritic cells (DCs) used as anticancer vaccine holds promise for therapy, but needs to be optimized. The most frequently described DC vaccine is being matured with a cocktail containing prostaglandin E2 (PGE2 DC). However, even though PGE2 DCs express both costimulatory and migratory receptors, their IL-12p70-prodcution is low, leading to an insufficient Th1 immune response. As an alternative, α-type-1 polarized DCs (αDC1s) have shown a superior production of IL-12p70 and subsequent activation of effector cells. From chronic lymphocytic leukaemia (CLL) patients, αDC1s can be generated to induce a functional Th1-immune response. Yet, another costimulatory receptor, CD70, appears to be essential for optimal DC function by promotion of T cell survival and function. So far, PGE2 is suggested as one of the most important factors for the induction of CD70 expression on DCs. Therefore, we wanted to investigate whether αDC1s have the ability to express functional CD70. We found that CD70 expression on αDC1s could be upregulated in the same manner as PGE2 DCs. In an allogeneic mixed leucocyte reaction, we found that antibody-blocking of CD70 on αDC1s from controls reduced effector cell proliferation although this could not be found when using CLL αDC1s. Nevertheless, CD70-blocking of αDC1s from both controls and patients with CLL had a negative influence on the production of both IL-12p70 and the Th1 cytokine IFN-γ, while the production of the Th2 cytokine IL-5 was enhanced. Together, this study further suggests that αDC1s should be considered as a suitable candidate for clinical antitumour vaccine strategies in patients with CLL.