measures of antigen-speciﬁc immune responses are needed (Keilholz et al 2002). Role of GM-CSF in supportive therapy Numerous clinical trials have established the role of CSF in the prevention and treatment of febrile neutropenia (Garcia- Carbonero et al 2001; Mizutani et al 2003; Repetto et al 2003). The majority of clinical trials investigated the role of G-CSF in the supportive care of cancer patients; therefore, the current recommendations do not address the speciﬁc use of GM-CSF in this setting. The American Society of Clinical Oncology (ASCO) has provided guidelines for the use of CSF (either G-CSF or GM-CSF) in patients receiving chemotherapy for solid and hematological malignancies (Smith et al 2006). No recommendation was made regarding the equivalency of G-CSF and GM-CSF. Rowe et al reported a signiﬁcant reduc- tion of infectious complications in patients with acute myeloid leukemia (AML) who received GM-CSF after induction che- motherapy, compared to placebo (Rowe et al 1995). However, Zittoun et al (2006) reported a decreased complete response (CR) rate in patients with AML who received GM-CSF with induction chemotherapy, indicating that the routine use of cytokines for acceleration of hematopoietic recovery may not always be indicated; and the use of CSF for priming of leukemic cells is not recommended. Dendritic cells as regulators of immune responses DC play a central role in the initiation of innate and adaptive immune responses. Pattern recognition receptors, known as toll-like receptors (TLR), on the surface of DC are bound by proteins, lipids, and nucleic acids resulting in DC activation (Kadowaki et al 2001; Dillon et al 2004). Antigen-speciﬁc T-cell immune responses are initiated by DC when these bound antigens are internalized, degraded, and presented as processed peptides on the surface of HLA molecules (Hart 1997; Bancereau and Steinman 1998; Banchereau et al 2000). Two main categories of peripheral blood and bone marrow derived DC have been described in humans, type 1, myeloid dendritic cells (DC1), and type 2 plasmacytoid dendritic cells (DC2) (Grouard et al 1997). DC1 and DC2 differ in the type of cell differentiation markers and TLR expressed on their surface, their cytokine milieu, and their effect on polarizing T-cell immune responses (Rissoan et al 1999; Amsen et al 2004; Dillon et al 2004). The maturation status of DC is an important determinant of the type of immune response gener- ated upon DC activation. For example, antigen presentation Biologics:Targets & Therapy 2008:2(1) Clinical uses of GM-CSF by immature DC leads to generation of anergic CD4+ T-cells (Kuwana et al 2001), and immuno-suppressive CD8+ T-cells with antigen-speciﬁcity (Gilliet and Liu 2002). Immature DC2 progenitors play a crucial role in the response to viral infection by releasing large amounts of alpha and beta interferon (Siegal et al 1999; Fonteneau et al 2003; Larsson et al 2003; Coccia et al 2004). The targeting of DC by synthetic TLR ligands is a topic of current clinical and pre-clinical research. Generation of dendritic cells by GM-CSF Colony-stimulating factors can differentiate hematopoietic progenitor cells into speciﬁc DC lineages (Santiago-Schwarz et al 1992; Grouard et al 1997; Olweus et al 1997; Rissoan et al 1999; Siegal et al 1999; Berthier et al 2000; Ferlazzo et al 2000). Hematopoietic stem cells cultured in GM-CSF and Flt3 can differentiate along a myelo-monocytic lineage into DC1 (Ferlazzo et al 2000). CD14+ progenitor cells cultured in GM-CSF and IL-4 can also differentiate into immature DC1 (Ferlazzo et al 2000; Basak et al 2002). In contrast, treat- ment of hematopoietic progenitors with G-CSF and IL-3 can mobilize large numbers of (plasmacytoid) DC2 (Arpinati et al 2000). Thus, while GM-CSF and G-CSF have similar effects on the mobilization of neutrophils, they have signiﬁcantly dif- ferent effects on the mobilization and differentiation of DC1 and DC2, with culture in GM-CSF leading to differentiation of progenitors into DC1, and culture in G-CSF leading to differentiation of progenitors into DC2 (Arpinati et al 2000). Due to their effects on DC1 and DC2, these 2 cytokines are optimal agents for cellular immune therapy. Cytokines and peripheral blood hematopoietic progenitor cell transplantation Peripheral blood as a source of stem cells for clinical stem cell transplantation was introduced by Korbling et al and Kessinger et al in the 1980s (Korbling et al 1981; Kessinger et al 1986). CSF are now widely used for the mobilization of hematopoietic progenitor cells into the peripheral circula- tion, allowing collection of CD34+ cells for autologous and allogeneic hematopoietic progenitor cell transplantation. Essential differences have been noted between bone marrow (BMT) and peripheral blood grafts, owing to differences in the ratio of early pluripotent, self-renewing stem cells to lineage- committed, late progenitor cells, and the accessory cells in the grafts (Korbling and Anderlini 2001). These differences may account for the observed differences in clinical outcomes after 15