Stromal cell–derived chemokines modulate immune cells in inflammation: New findings and future perspectives

Tissue stromal cells are composed of numerous cell types with phenotypical and functional heterogeneity. Apart from providing structural support, they are emerging as key orchestrators of both activation and repression of immune responses in tissue microenvironment. The underlying mechanisms by which stromal cells contribute to immunomodulation are multifaceted, in which the chemokine-mediated interactions with immune cells have drawn great attention. The distinct stromal cell subpopulations can change the chemokine secretion profiles to regulate the recruitment and activation of immune cells in the onset and progression of inflammation. Elucidation of the mechanisms of the homeostatic and pathogenic stromal-immune cell interactions via chemokines can assist in the identification of novel therapeutic targets for modulating inflammatory diseases and enhancing the efficacy of cancer immunotherapy. Therefore, the current review highlights the updated understanding of the stromal-immune interactions via chemokines in inflammation, as well as potential therapeutic avenues to target at the intercellular crosstalk for inflammatory disorders and cancer.