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Chemokine Receptors Signaling Pathways  Chemokines & Chemokine Receptors

The chemokines are a chemotactic cytokines that function by binding to seven-transmembrane-spanning G protein-coupled receptors (Chemokine Receptors).

These receptors are divided into those that preferentially bind CXC or CC chemokines, and are capable of binding more than one CC or CXC chemokine, respectively (1,4). Chemokines play a crucial role in the development and homeostasis of the immune system, inflammation, directed and undirected motility of cells, most notably white blood cells (leukocytes). These molecules and their receptors can trigger diverse cellular migratory responses such as haptokinesis, haptotaxis, and chemokinesis, including inducing cell adhesion and cell arrest (1,2,5).

Chemokines and chemokine receptors involved in immune activation and immune inhibition: The different cells in tumour microenvironment are infiltrated and activated by different chemokines. These cells can be immunoactivatory or immunoinhibitory in nature. A number of such chemokines and chemokine receptors are shown that affect the cancer immune response (2)

Receptors of chemokines play a role in chemotaxis and initiating cell trafficking to the desired location by trigger a flux of calcium ions intracellularly upon specific ligand binding. They are classified into four subfamilies based on structural and functional criteria: CC, CXC, CX3C and C. CC and CXC chemokines, for instance, play key roles in angiogenesis, leukocyte recruitment, and tumour growth and proliferation (2).

Chemokine Receptors Signaling Pathways  Chemokines and Chemokine Receptors in diseases

Chemokines are recognized to play key roles in the pathogenesis of inflammatory and autoimmune diseases ( exp; atherosclerosis, …), coronavirus infection, tumor progression, … Some of these molecules primarily have anti-tumor effects, while others typically have pro-tumor responses (2,3,4). Various studies describe the role of chemokines in enhancing cancer cell properties, such as chemokines supporting tumor growth and proliferation, epithelial to mesenchymal transition, cancer stem cell properties, and resistance to chemotherapy (5).
(1) Hughes CE, Nibbs RJB. A guide to chemokines and their receptors. FEBS J. (2018);285(16):2944-2971.
(2) Braoudaki M, et al. Chemokines and chemokine receptors in colorectal cancer; multifarious roles and clinical impact. Semin Cancer Biol. (2022);86(Pt 2):436-449.
(3) Gencer S, et al. Inflammatory Chemokines in Atherosclerosis. Cells. (2021);10(2):226.
(4) Olivarria G, Lane TE. Evaluating the role of chemokines and chemokine receptors involved in coronavirus infection. Expert Rev Clin Immunol. (2022);18(1):57-66.
(5) Saxena S, Singh RK. Chemokines orchestrate tumor cells and the microenvironment to achieve metastatic heterogeneity. Cancer Metastasis Rev. (2021);40(2):447-476.
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