%0 Journal Article
%T The key role of CD40 ligand in overcoming tumor-induced dendritic cell dysfunction
%A Alberto Pinzon-Charry
%A Chris W Schmidt
%A Jos¨¦ L¨®pez
%J Breast Cancer Research
%D 2005
%I BioMed Central
%R 10.1186/bcr1386
%X Crucial to the role of dendritic cells (DCs) as immune sentinels is their capacity to interact with lymphocytes [1]. This interaction mediates bi-directional signaling; DCs activate T lymphocytes (both CD4 and CD8) in an antigen-specific fashion and also receive signals from activated T lymphocytes (CD4) via CD40L [2]. Indeed, the most efficient activation of cytotoxic CD8 lymphocytes required for tumor clearance seems to be the result of DC licensing after the interaction between CD40 and its ligand [3].In this issue of Breast Cancer Research we show that patients with breast cancer exhibit a high rate of spontaneous apoptosis of circulating DCs [4]. Lenahan and Avigan [5] comment on our report, highlighting the protective function of IL-12 and CD40L against tumor-induced apoptosis. They suggest that the increased susceptibility of blood DCs to apoptosis might result in a diminished capacity of patients to respond to vaccines that depend on in vivo loading of DCs and recommend the use of DCs conditioned ex vivo to circumvent this problem. One alternative is the use of adjuvant cytokines or CD40L to treat DCs. Indeed, in vitro stimulation with CD40L has been demonstrated to enhance the efficiency of DCs as antigen-presenting cells (APCs) for anti-tumoral immunization [6].From an immunotherapy perspective such data are particularly relevant because DC-based therapies are being evaluated as vaccine adjuvants and are therefore being aggressively pursued in the treatment of a wide range of malignancies including breast cancer [7]. The design of DC vaccines to prevent the recurrence or achieve the regression of already existing tumors has been a major goal of immunotherapy. Blood DCs have been proposed for immunotherapy protocols because they offer the theoretical advantage of being in their natural state of differentiation and are thus capable of orchestrating immune responses in a more physiological manner.Given that tumors are suppressive to DCs and induce significant
%U http://breast-cancer-research.com/content/8/1/402