Chemokines and Cancer: Friends or Foes?

Abstract

Immune cell infiltration into tumors, intratumoral cellular organization, and the cell-specific expression patterns of chemokines and chemokine receptors greatly influence the efficacy of immunotherapeutic treatment strategies. In our recent review article, we shined a light on the deciding role of the chemokine network between immune mediated tumor regression or immune evasion of the tumor. Current T cell centric immunotherapeutic strategies primarily rely on increasing cellular activation and decreasing cellular inhibition, with the overall goal of enhancing effector cell function. These strategies neglect to account for the presence of the T cells within the tumor, hardly boosting immune cell infiltration. Chemokines and chemokine receptors are the regulators of recruitment, migration, and intratumoral compartmentalization. Yet, utilizing the chemokine network to recruit immune cells that will drive tumor regression is not a straightforward path, as tumor cells often hijack these pathways in the effort of immune evasion. Many novel therapeutic strategies involving chemokine targeting are under trial for many diverse tumor types. As a field, we can learn from both the successes and failures of these trials in order to push forward the next generation of immunotherapeutic strategies that include augmented T cell trafficking.