Abstract
The innate and adaptive immune systems have evolved together to fight infection and cancerous tissues. The innate immune system emerges first with the adaptive immune system following, both ostensibly being bridged by dendritic cells (DC). Recently cells have emerged that possess characteristics of both innate and adaptive immune cell qualities, termed interferon-producing killer dendritic cells (IKDCs). These cells have an indistinct origin that is not well understood. They appear to have more NK cell attributes than DC but purportedly can regulate the immune system similar to immunoregulatory NK cells. Because of this, they have been renamed pre-mNK cells (pre-mature NK cells). We argue in this commentary that pre-mNK cells may contribute to cancer recurrence.
Highlights
Pre-mature Natural Killer cells are murine hybrid cells with characteristics of both NK cells and dendritic cells (DC), defined by markers CD11c+CD49b+B220+NK1.1 +NKG2D+GR-1− and expressing MHC class II upon activation [1,2,3,4] (Fig. 1)
We showed that B220+ cell depletion but not asialo-GM1+ cell depletion was similar to the depletion of NK1.1+ cells, suggesting that B220+NK1.1+ Pre-mature Natural Killer cells (pre-mature NK (mNK)) cells were playing a role in dampening the CD4+ anti-tumor response in our preclinical model of melanoma [11]
As others have implicated, that pre-mNK cells must be licensed by tumor cells through NKG2D or other ligands to become activated [3, 21]
Summary
Pre-mature Natural Killer cells (pre-mNK) are murine hybrid cells with characteristics of both NK cells and DC, defined by markers CD11c+CD49b+B220+NK1.1 +NKG2D+GR-1− and expressing MHC class II upon activation [1,2,3,4] (Fig. 1). These types of experimental systems used to study these cells in vitro, we would argue, can be highly non-physiologic and may drive HLA-DR+ NK cells to a cytotoxic phenotype, leading to large amounts of IFN-γ secretion Their physiological role in vivo without external activation may involve tolerance mechanisms as these cells are seen at sites of inflammation, cancer, and at the maternal-fetal interface [47,48,49,50,51,52]. This may be similar to pre-mNK cell activation through NKG2D ligands on murine tumors, allowing them to present antigen once it is acquired [3] They can be lytic, it has been shown that in both the viral and the autoimmune setting that CD56bright NK cells control CD4+ T cell activity by expressing high levels of CD39/73 and CD38, using adenosine as a modulator of T cell activity. Morandi et al report that CD38 inhibition increases Juvenile Idiopathic Arthritis (JIA) severity, while the CD38 enzyme expressed by CD56bright NK cells in patients with active JIA has attenuated function [56]
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