Abstract
Interferon-producing killer dendritic cells (IKDC) were first described for their outstanding anti-tumoral properties. The “IKDC” terminology implied the description of a novel DC subset and initiated a debate on their cellular lineage origin. This debate shifted the focus away from their notable anti-tumoral potential. IKDC were recently redefined as precursors to mature NK (mNK) cells and consequently renamed pre-mNK cells. Importantly, a putative human equivalent of pre-mNK cells was recently associated with improved disease outcome in cancer patients. It is thus timely to revisit the functional attributes as well as the therapeutic potential of pre-mNK cells in line with their newly defined NK-cell precursor function.
Highlights
The immune system forms an elaborate network of multiple cell types which together collaborate to eliminate unwanted pathogens and tumor cells
As the debate on the lineage origin comes to a close, the means by which pre-mature natural killer (NK) (mNK) cells carry out the elimination of tumors needs to be revisited
The adoptive transfer of BM-derived pre-mNK cells could inhibit 76.9 tumor growth in B6 mice but not in immunodeficient tumor-bearing host mice showing that BM-derived premNK cells are dependent on the presence of the adaptive immune system for tumor rejection, again supporting their role in antigenpresentation [23, 59]. These results contrast with those showing anti-tumoral activity of pre-mNK cells in Rag2−/−Il2rg−/− mice carrying established melanomas, suggesting that BM-derived premNK cells may have different migratory or functional properties to that of pre-mNK cells isolated from a spleen [22]
Summary
The immune system forms an elaborate network of multiple cell types which together collaborate to eliminate unwanted pathogens and tumor cells. The type of mNK cells generated from each of these distinct pathways, as well as the specific cellular intermediates, such as CD127+-thymic-derived NK cells and pre-mNK cells, may play specific roles in the immune response. Additional in vitro and in vivo manipulations of pre-mNK cells have revealed that the cytotoxic activity toward tumoral cells and the antigen-presentation potential to T cells are likely to be uncoupled.
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