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Acetylcholine Nicotinic Receptors, Non-selective

Immunotherapy represents a promising new avenue for the treatment of multiple myeloma (MM) patients, particularly with the availability of Monoclonal Antibodies (mAbs) as anti-CD38 Daratumumab and Isatuximab and anti-SLAM-F7 Elotuzumab

Immunotherapy represents a promising new avenue for the treatment of multiple myeloma (MM) patients, particularly with the availability of Monoclonal Antibodies (mAbs) as anti-CD38 Daratumumab and Isatuximab and anti-SLAM-F7 Elotuzumab. multiple myeloma 1. Introduction Natural killer cells are a group of innate lymphoid cells (ILCs) with strong cytotoxic function against stressed cells, such as virus-infected cells or tumor cells. They represent 5C15% of human peripheral blood mononuclear cells (PBMC) and tissue-resident NK cells can be found in the skin, spleen, liver, lungs, and other organs under physiological conditions [1]. NK cells in the blood appear as large lymphocytes with numerous cytoplasmic granules and can be distinguished from other lymphoid cells by the absence of T- and B-cell-specific markers, such as CD3 and CD19, and the presence of neural cell adhesion molecule (NCAM) CD56. Two main human NK cell subsets can be distinguished based on CD56 density on the cell surface: CD56bright and CD56dim. CD56bright NK cells are Rabbit Polyclonal to Akt the major subset of NK cells in secondary lymphoid tissues and represent a less mature stage of NK cell differentiation, whereas CD56dim cells represent the majority of NK population in the peripheral blood (80C95%) [2]. The downregulation of CD56 is associated with the acquisition of a high cytotoxic potential and this reflects the distinct physiological roles of the two NK cell subsets: CD56bright population is specialized in the production of inflammatory cytokines and chemokines, while the cytotoxic function resides primarily in CD56dim cells [3]. The different functions of CD56bright and CD56dim populations also reflect the presence of distinct NK receptors and other molecules on the surface of the two subsets including CD16, which is expressed on most CD56dim cells and in a limited subset of CD56bright cells. 1.1. Development and Maturation of NK Cells Human NK cells develop primarily in the BM and, unlike T Morinidazole cells, do not require thymus for their maturation. However, subsets of NK cells have been shown to develop in secondary lymphoid organs, including lymph nodes and thymus, and in the liver [4,5]. NK cell development in the Morinidazole BM from the common lymphoid progenitor (CLP) proceeds through distinct maturation stages still not completely characterized based on sequential acquisition of NK cell-specific markers and functional competence. Expression of Morinidazole CD122 (IL-2R) marks the irreversible commitment of CLPs into NK lineage, while the appearance of CD56 indicates a final transition from immature NK cells to mature NK cells, together with the expression of CD57 Morinidazole as a marker of terminal differentiation. Downregulation of CD56 expression from bright to dim levels marks the final differentiation stages and is associated with the appearance of CD16 receptor (FcRIII). Several cytokines are essential to NK cell survival. In particular, IL-15 was shown to be crucial for the growth of NK cells and for the homeostasis and survival of peripheral NK cells. IL-2, IL-7 and IL-21 have important, albeit less characterized, roles in sustaining NK cell proliferation and survival, as well [6]. During their development, NK cells undergo an educational process involving the engagement of inhibitory Morinidazole killer immunoglobulin receptors (KIRs) with cognate MHC class I molecules. Inhibitory KIR expression during NK cell development is essential for the establishment of the missing-self recognition, a process by which NK cells preferentially recognize and kill cells that have lost the expression of self MHC class I molecules. The number of interactions between inhibitory receptors on developing NK cells and MHC class I molecules on stromal and hematopoietic cells in the bone marrow determines the degree of responsiveness of mature NK cells. In contrast, NK cells that lack inhibitory receptor expression during their development or are unable to interact with MHC class I molecules become hyporesponsive (anergic) cells [4]. This mechanism allows for the self-tolerance of.