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Fig. 2 | Cancer Cell International

Fig. 2

From: NK cell upraise in the dark world of cancer stem cells

Fig. 2

NK cell, from development to Functioning. A The pathway of NK cell generation and development; NK cells are derived from common lymphoid progenitor (CLP), and then enter the NK cell precursors (NKP) stage that express IL-7R and IL-2Rß 2Rß and IL-15 which play crucial roles in NK cells differentiation from CLPs to mature NK cells. These cells then express NKR-P, CD2, CD56, CD94 and KIRs and go through maturity and get ready for function. Mature NK cells also gain functional competence, expressing lytic molecules and cytokines such as Perforin, Granzyme A/B and IFN-γ. B NK cell educating and function; NK cells disappear from blood either by entering tissues, predominantly the spleen and the liver or through cell death. CD56bright NK cells proliferate fast, but die relatively slowly which suggests that proliferating CD56bright cells differentiate into CD56dim NK cells in vivo. The peak of the effector NK cell expansion occurs at around 7–8 days after activation, regardless of the precursor frequency of antigen-specific NK cells, however it is difficult to detect memory NK after 4–5 months although they still exist. NK cells depict three mechanisms for their function on the target cells in 3 different pathways; 1. Missing-self in which the inhibitory receptors of MHC-I molecules are involved, and the cells are lysed in the down-regulation of MHC class I molecules, 2. Induced self-ligands in which NK cell activating receptors can detect stress molecules that are overexpressed by tumor cells, and ultimately lysing the target cell, 3. Antibody-dependent NK cell-mediated cytotoxicity in which specific antibodies of tumor antigens are binding to CD16 and subsequently cause the target cell to lyse (21, 22). C NK cells can play modulatory role in the immune system against tumor and infected cells, and affect T cells and macrophages and prepare them to serve, and also have a significant contribution to the process of maturation of dendritic cells. HSCs hematopoietic stem cells; mNK cell, mature NK cell

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