CD56+ human blood dendritic cells: unique mediators of strong natural killer and gamma/delta T cell activation to promote antigen-specific T cell immune responses in health and disease.

Human blood contains several immune-competent cells including cells of the innate and adaptive immune system. Over the past years, the phenotypic and functional boundaries distinguishing the main cell subsets of the immune system have become increasingly blurred. While it has been already established that T cells may share some phenotypic and functional features of natural killer (NK) cells, more recent evidence points to the existence of such overlap between NK cells and dendritic cells (DCs). Both NK cells bearing DC markers and antigen-presenting capacity and DCs expressing NK-related molecules and having cytotoxic functions have been described. In view of this, CD56, a prototypic marker of NK cells, was found to be expressed on DC derived from monocytes exposed to interleukin-15. We demonstrated that these IL15-DC were endowed with superior stimulatory and unique cytotoxic properties (killer DC). The aim of this project is to identify and characterize in detail the in vivo counterpart of these CD56+ killer DCs in human blood. Particular emphasis will be given to the reciprocal interactions of myeloid CD56+ DC-like cells with CD56+ innate lymphocytes (NK and NKT cells, γδ T cells) in the presence or absence of immunomodulatory molecules. Next, the capacity of CD56+ blood DCs to stimulate both innate and adaptive cell responses will be analyzed in a human acute myeloid leukemia (AML) model as a first step towards design of next-generation therapeutic AML vaccines.

Keywords:CANCER VACCINES, MRNA ELECTROPORATION, DENDRITIC CELLS, ACUTE MYELOID LEUKEMIA

Disciplines:Immunology, Morphological sciences, Oncology