High Functional CD70 Expression on alpha-Type 1-Polarized Dendritic Cells from Patients with Chronic Lymphocytic Leukaemia
2014 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 79, no 6, 415-422 p.Article in journal (Refereed) Published
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 (PGE2DC). However, even though PGE2DCs express both costimulatory and migratory receptors, their IL-12p70-prodcution is low, leading to an insufficient Th1 immune response. As an alternative, -type-1 polarized DCs (DC1s) have shown a superior production of IL-12p70 and subsequent activation of effector cells. From chronic lymphocytic leukaemia (CLL) patients, DC1s 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 DC1s have the ability to express functional CD70. We found that CD70 expression on DC1s could be upregulated in the same manner as PGE2DCs. In an allogeneic mixed leucocyte reaction, we found that antibody-blocking of CD70 on DC1s from controls reduced effector cell proliferation although this could not be found when using CLL DC1s. Nevertheless, CD70-blocking of DC1s from both controls and patients with CLL had a negative influence on the production of both IL-12p70 and the Th1 cytokine IFN-, while the production of the Th2 cytokine IL-5 was enhanced. Together, this study further suggests that DC1s should be considered as a suitable candidate for clinical antitumour vaccine strategies in patients with CLL.
Place, publisher, year, edition, pages
2014. Vol. 79, no 6, 415-422 p.
Immunology in the medical area
IdentifiersURN: urn:nbn:se:uu:diva-228725DOI: 10.1111/sji.12172ISI: 000337588500009OAI: oai:DiVA.org:uu-228725DiVA: diva2:734771