Role of NK cells, Chemokines, and Pyroptosis in Melanoma Development or Treatment
Dr. Azzam A. Maghazachi E-Mail
Professor, College of Medicine, and Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE
Research Keywords: autoimmune diseases, immunology, chemokines, cancer immunotherapy, drug mechanisms of action (MOA)
This issue will deal with the effects of cells, molecules and processes in the development, progression or treatment of Melanoma.
The Cells: Natural killer (NK) cells are innate immune cells that serve as anti-tumor effectors which have been used for the treatment of various cancers. These cells have two major functions that are crucial for eradication of stressed cells as well as communication with innate and adaptive immunity. Upon cell-to-cell contact, an immunological synapse forms, along with the rearrangement of the actin cytoskeleton and cytolytic granules containing perforin and granzymes, which are polarized towards the target cell. Perforin is a pore forming protein that facilitates the entry of the granzymes into the target cell cytoplasm, where they perform their function as serine proteases, cleaving intracellular proteins. NK cell function is tightly regulated by a repertoire of membrane-expressed inhibitory and activating receptors. NK cell inhibitory receptors include members of the C-type lectin-like receptor family such as the NKG2A/CD94 heterodimer and the killer immunoglobulin-like receptors (KIR). On the other hand, activating receptors recognize altered self-antigens that are expressed on stressed cells which act as danger signals. The major activating receptors include NKG2D as well as several natural cytotoxicity receptors (NCRs) such as NKp30, NKp44, and NKp46]. Activation of NK cells occurs when the threshold of activating signals exceeds the inhibitory ones.
The Molecules: Chemokines are chemotactic cytokines, that are comprised of 70–130 amino acids, with a molecular weight of 8 to 14 kDa. Chemokines exert their functional activities by binding to classical chemokine receptors, which belong to the seven transmembrane G protein coupled receptor (GPCR) family. According to the expression of these receptors, chemokines perform their various functions including promoting cell migration. Chemokines are structurally divided into 4 groups according to their cysteine residues, namely, C, CC, CXC, and CX3C. Several chemokines are known to have an impact on the proliferation and survival of cancer cells. For instance, CXCR6, CCR6, CCR7 and CCR10 promote the proliferation and survival of tumors such as that observed in prostate cancer, colorectal cancer, head and neck squamous cell carcinoma as well as Melanoma.
The Process: Pyroptosis is a programmed cell death with inflammasome formation, resulting in the synthesis and release of active proinflammatory cytokines, which include IL-1β and IL-18. Gasdermin D is the mediator of Pyroptosis, forming pores in the membranes which aid the secretion of these inflammatory mediators that play important roles in health and diseases. The role of Pyroptosis and/or Gasdermin D in the development and progression of melanoma is not clear yet.
We welcome all research or review articles investigating the roles play by NK cells, Chemokines and/or Pyroptosis in Melanoma development, progression or treatment.
Keywords: melanoma, NK cells, chemokines, pyroptosis