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High Functional CD 70 Expression on α ‐Type 1‐Polarized Dendritic Cells from Patients with Chronic Lymphocytic Leukaemia
Author(s) -
Junevik K.,
Werlenius O.,
Fogelstrand L.,
KarlssonParra A.,
Andersson P.O.
Publication year - 2014
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12172
Subject(s) - immune system , receptor , blocking antibody , downregulation and upregulation , immunology , dendritic cell , effector , cytokine , antigen , t cell , chemistry , cancer research , biology , medicine , biochemistry , gene
Antigen‐loaded dendritic cells ( DC s) 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 E 2 ( PGE 2 DC ). However, even though PGE 2 DC s 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 DC s ( α DC 1s) have shown a superior production of IL ‐12p70 and subsequent activation of effector cells. From chronic lymphocytic leukaemia ( CLL ) patients, α DC 1s can be generated to induce a functional Th1‐immune response. Yet, another costimulatory receptor, CD 70, appears to be essential for optimal DC function by promotion of T cell survival and function. So far, PGE 2 is suggested as one of the most important factors for the induction of CD 70 expression on DC s. Therefore, we wanted to investigate whether α DC 1s have the ability to express functional CD 70. We found that CD 70 expression on α DC 1s could be upregulated in the same manner as PGE 2 DC s. In an allogeneic mixed leucocyte reaction, we found that antibody‐blocking of CD 70 on α DC 1s from controls reduced effector cell proliferation although this could not be found when using CLL α DC 1s. Nevertheless, CD 70‐blocking of α DC 1s 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 α DC 1s should be considered as a suitable candidate for clinical antitumour vaccine strategies in patients with CLL .