Killer dendritic cells: mechanisms of action and therapeutic implications for cancer

Top of pageAbstract Dendritic cells (DC) are essential for the development and regulation of adaptive host immune responses against tumors. DC are heterogeneous and comprised of diverse cellular subsets. They are best known for mediating a crucial role in the initiation of acquired immunity by serving as professional antigen presenting cells (APC) that take up antigens in their local microenvironment, which are then processed and presented to naive T cells in the context of major histocompatibility complex (MHC) class I and II molecules. In addition to these functions, DC can modulate the types of T cell responses they generate, and can also influence the responses of innate effectors, such as NK cells. There is also now evidence that they may mediate a more primordial role as innate, effector cells that are tumoricidal. ‘Killer’ DC (KDC) may represent a true ‘multi-tasking’ cell type that can sequentially act as a ‘hunter-gatherer’ of antigens; as well as, an instructor, then enforcer/regulator, of antigen-specific anti-tumor T-cell responses in vivo. In this review, we will critically examine the published record regarding KDC, their mechanism(s) of action, and then consider the potential integration of KDC into novel immunotherapies for patients with cancer. Keywords: dendritic cells (DC), cytotoxicity, apoptosis, tumor cells, killer cells Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; BM-DC, bone marrow-derived DC; CFSE, 5-(and -6)-carboxyfluorescein diacetate succinimidyl ester; DC, dendritic cell; IFN, interferon; IKDC, interferon-producing killer DC; iNOS, inducible nitric oxide synthase; KDC, killer DC; LCMV, lymphocytic choriomeningitis virus; LT, lymphotoxin; MDC, myeloid DC; Mono-DC, monocyte-derived DC; NK, natural killer; NKDC, natural killer DC; ODN, oligodeoxynucleotides; pDC, plasmacytoid DC; TLR, toll-like receptor; TNF, tumor necrosis factor; TRAIL, tumor necrosis (TNF)-related apoptosis-inducing ligand