The Complexity of Targeting Chemokines to Promote a Tumor Immune Response

Immunotherapeutic treatment strategies greatly extend patient survival following malignant disease across a wide range of tumor types, including even those with metastatic disease. While diverse in approach, adoptive cell therapy, introduction of T cells that express chimeric antigen receptors, and checkpoint inhibitors all aim to re-invigorate the immune system to promote tumor cell identification and elimination. This review will focus on immune cell infiltration into tumors as well as a cellular organization within the tumor microenvironment as directed by the cell-specific expression patterns of chemokines and chemokine receptors. Through better understanding the chemokine network within tumors, we can uncover mechanisms to promote beneficial immune cell infiltration that can be combined with checkpoint inhibition. Conversely, chemokine expression is not limited to cells of the immune system, and it is understood that tumor cells also express chemokines and chemokine receptors. Tumor cells can hijack the chemokine networks to promote immune suppression and metastatic tumor cell trafficking. We will discuss the ways in which the chemokine network lies at the crossroad of immune evasion and tumor regression. Overall, this review will summarize key publications in the field of immune cell recruitment to tumors, highlight the dichotomous nature of chemokine interventions into cancer, and aims to identify therapeutic pathways forward.