Chemokine-chemokine receptors in cancer immunotherapy

摘要

Chemokines (chem.0t2.ctic cytokines) were initially described as small secretory proteins that were involved in the activation and recruitment of immune cells during an inflammatory response. It is now known that they have many roles, including in homeostasis, cell proliferation, hematopoiesis, host-virus interactions and angiogenesis [1]. An important function for the purposes of this review is their role in the migration, survival and growth of cancer cells; as well as the regulation of tumor angiogenesis and leukocyte recruitment. The major role of chemokines is to direct the migration of cells via increasing concentration gradients towards the source of the chemokine. Chemokines are classified based on their small size and the presence of four cysteine residues, which occur at conserved locations and are key to forming their 3D tertiary structures. They range in size from 8 to 11 kDa in molecular weight and are active over a 1-100-ng/ml concentration range. Four classes of chemokines have been defined based on the location of the first two cysteine residues within the protein sequence (CXC, CC, C and CX_3C) (Table1). Most chemokines are secreted proteins of between 67 and 127 amino acids; with only the CXCL16 and CX3CL1 chemokines being membrane bound. A typical chemokine protein is produced as a propeptide that has an approximate 20 amino acid segment that is cleaved from the active portion of the molecule during the secretion process. Chemokines can be immobilized on cell surfaces or extracellular matrices by binding to glycosaminoglycans [2].