Chemokine family proteins

Chemokine network in the tumoral microenvironment immune response

Chemokines are small cytokines or signaling proteins secreted by cells. According to the number and arrangement of conserved L-Cysteine (C) at the N-terminal, chemokines can be classified into four classes: C, CC, CXC and CX3C. These chemokines signal through the seven-pass transmembrane chemokine receptor of G-protein coupling on the cell surface, which stimulate the cell directional migration. Homeostatic chemokines are constitutively expressed under physiological conditions and play a role in cell migration and homing, whereas inflammatory chemokines are rapidly secreted at sites of inflammation, thereby recruiting effector cells into inflamed tissues. Thus, chemokines play a central role in the development and homeostasis of the immune system and are involved in promoting the activation, differentiation, proliferation and apoptosis of immune cells and in all protective or destructive immune and inflammatory responses.

Furthermore, chemokine signaling and the chemotaxis of various cell populations also play a central role in the tumor microenvironment (TME). In the TME, many chemokines are released by immune cells, tumor cells and tumor-associated cells. These chemokines can change with time and space, attracting different types of tumor-promoting and anti-tumor immune cells. The migration of immune cells will further affect the progression and metastasis of tumors, and directly affect the immune response. Studies have revealed that chemokines have pleiotropic functions that affect anti-tumor immune responses and tumor progression. With this in mind, therapeutic strategies that utilize or target chemokines have been established over the past decade, leading to the testing of many new drug candidates in clinical trials. Notably, in chemokine-based therapies, chemokines are highly redundant in binding to receptors, the same receptor can bind to different chemokines, and vice versa. Therefore, only by simultaneously inhibiting chemokine and its receptor with the same physiological function can the therapeutic effect be healthier and lasts longer.