Chemokine signaling in cancer-stroma communications

Abstract

Cancer is a multi-faceted disease in which spontaneous mutation(s) in a cell leads to the growth and development of a malignant new organ that if left undisturbed will grow in size and lead to eventual death of the organism. During this process, multiple cell types are continuously releasing signaling molecules into the microenvironment, which results in a tangled web of communication that both attracts new cell types into and reshapes the tumor microenvironment as a whole. One prominent class of molecules, chemokines, bind to specific receptors and trigger directional, chemotactic movement in the receiving cell. Chemokines and their receptors have been demonstrated to be expressed by almost all cell types in the tumor microenvironment, including epithelial, immune, mesenchymal, endothelial, and other stromal cells. This results in chemokines playing multifaceted roles in facilitating context-dependent intercellular communications. Recent research has started to shed light on these ligands and receptors in a cancer-specific context, including cell-type specificity and drug targetability. In this review, we summarize the latest research with regards to chemokines in facilitating communication between different cell types in the tumor microenvironment.

Keywords: Cancer; Chemokines; Review; Tumor microenvironment.

Fig. 1

Small representation of the TME with a focus on communication between cancer and immune cells. Cancer cells express high levels of many different chemokines and receptors, whereas immune cells express more specific chemokines and receptors, depending on the cell subtype. Frequently it is chemokines secreted my cancer cells that initially attract immune cells into the TME. It should be noted that this is not a comprehensive cartoon, since the expression of certain chemokines and ligands can be context and environment dependent. CD8: CD8 + T-cell; TAM: tumor-associated macrophage; NK: Natural Killer Cell; NT: Neutrophil; Treg: Regulatory T-cell; MON: Monocyte; MDSC: Myeloid-derived Suppressor Cell

Fig. 2

Small representation of the TME with a focus on communication between fibroblast/mesenchymal stromal cells and immune cells. Fibroblasts express high levels of many different chemokines, but express very few receptors. Frequently it is chemokines secreted by cancer cells and fibroblasts that initially attract immune cells into the TME. It should be noted that this is not a comprehensive cartoon, since the expression of certain chemokines and ligands can be context and environment dependent. MSC/FB: Mesenchymal Stromal Cell / Fibroblast; CD8: CD8 + T-cell; TAM: tumor-associated macrophage; NK: Natural Killer Cell; NT: Neutrophil; Treg: Regulatory T-cell; MON: Monocyte; MDSC: Myeloid-derived Suppressor Cell

Fig. 3

Small representation of the TME with a focus on communication between fibroblast/mesenchymal stromal cells, cancer cells, and endothelial cells. Endothelial cells express few and very specific chemokines and receptors, relative to fibroblasts and cancer cells. It should be noted that this is not a comprehensive cartoon, since the expression of certain chemokines and ligands can be context and environment dependent. MSC/FB: Mesenchymal Stromal Cell / Fibroblast