Moreover, their guiding of rare tumour-specific CD8+ T cells to sites of DC–CD4+ T cell interactions by secretion of CCL3 and CCL4 is needed. We therefore analysed the chemokine mTOR inhibitor profile and the lymphocyte-attracting ability in vitro of monocyte-derived PGE2DCs and αDC1s from patients with CLL. αDC1s produced much higher levels of CXCR3 ligands (CXCL9/CXCL10/CXCL11) than PGE2DCs. Functional

studies further demonstrated that αDC1s were superior recruiters of both NK and NKT cells. Moreover, αDC1s produced higher levels of CCL3/CCL4 upon CD40 ligation. These findings suggest that functional αDC1s, derived from patients with CLL, produce a desirable NK-, NKT- and CD8+ T cell-attracting chemokine profile which may favour a guided and Th1-deviated priming of CD8+ T cells, supporting the idea that αDC1-based vaccines have Erlotinib manufacturer a higher immunotherapeutic potential than PGE2DCs. Chronic lymphocytic leukaemia (CLL) has traditionally been considered an incurable disease [1], which seems to hold true even in the era of

immunochemotherapy. Yet, complete molecular remissions and long-term disease-free survival are seen after allogeneic stem cell transplantation (alloSCT), providing evidence of a graft-versus-leukaemia effect and thus suggesting the possibility of an immune-mediated cure for CLL [2, 3]. However, procedure risks (i.e. non-relapse mortality and severe chronic graft-versus-host disease), patient age and, in many cases, patient co-morbidity makes alloSCT a possible treatment option only for a minority

of patients with CLL. Still, the strong antitumour response seen after alloSCT implies that CLL could be an attractive target for other less toxic immunotherapeutic strategies. Dendritic cells (DCs) have a unique ability to efficiently present antigens to naïve T cells and are key players in the initiation and regulation of innate and adoptive immune responses [4]. There are several preclinical studies regarding ex vivo-generated DCs as potential vaccines against CLL [5–10] because this could be a strategy to circumvent the immune defects [11] and the reported dipyridamole dysfunction of DCs in patients with CLL [12]. However, to enable T helper 1 (Th1) and cytotoxic T cell (CTL) induction and antitumour responses in vivo, a DC has to present relevant tumour antigens in combination with costimulatory molecules [13]. Of major importance is also the production of IL-12p70, known to polarize the immune response towards a Th1 response which is crucial for the induction of tumour-specific CTLs [14, 15]. However, the ability of injected vaccine DC to induce a Th1-polarized immune response in vivo most likely relies on additional features. Of potential importance is a chemokine secretion pattern, recently shown to be imprinted during DC maturation [16, 17], that should favour the recruitment of NK and probably also NKT cells into the vaccine-draining lymph node while avoiding interaction with regulatory T cells [18, 19].