Consider the Chemokines: a Review of the Interplay Between Chemokines and T Cell Subset Function

Subsets of T cells can be classified by the functions executed or by the anatomic location at which they operate. In vitro analysis of T cell subsets and even commercial kits for subset separation often incorporate chemokine receptors into the panel of markers to distinguish among them, but what is the functional significance of these receptors? In this review, we discuss chemokine receptors that are expressed exclusively on different T cell subsets as well as those that are commonly expressed across subsets with the goal of linking receptor expression to cellular localization and intended cellular function. By understanding the chemokine network, we can better predict T cell migration and the immune reactivity of a given tissue environment. This is of particular importance for the chemokine expression patterns of solid tumor microenvironments as it relates to T cell infiltration. A successful immunotherapeutic strategy needs to incorporate not only the activation state of cytotoxic T cells but also the likelihood that these cells come into contact with tumor cells. We highlight what is currently known about chemokine expression by tumors of various origins and how this relates to immune suppression or activation. Chemokine signaling represents a promising area of potential anti-tumor intervention and the current state of agonists or antagonists is discussed. Overall, this review relates chemokine signaling to T cell function and emphasizes the importance of chemokines and chemokine receptors in tumor infiltration by T cells.