Physiology of chemokines in the cancer microenvironment

Author:

Drouillard Donovan12ORCID,Craig Brian T.23,Dwinell Michael B.243ORCID

Affiliation:

1. Medical Scientist Training Program, Medical College of Wisconsin, Milwaukee, Wisconsin

2. Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin

3. Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin

4. Center for Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin

Abstract

Chemokines are chemotactic cytokines whose canonical functions govern movement of receptor-expressing cells along chemical gradients. Chemokines are a physiological system that is finely tuned by ligand and receptor expression, ligand or receptor oligomerization, redundancy, expression of atypical receptors, and non-GPCR binding partners that cumulatively influence discrete pharmacological signaling responses and cellular functions. In cancer, chemokines play paradoxical roles in both the directed emigration of metastatic, receptor-expressing cancer cells out of the tumor as well as immigration of tumor-infiltrating immune cells that culminate in a tumor-unique immune microenvironment. In the age of precision oncology, strategies to effectively harness the power of immunotherapy requires consideration of chemokine gradients within the unique spatial topography and temporal influences with heterogeneous tumors. In this article, we review current literature on the diversity of chemokine ligands and their cellular receptors that detect and process chemotactic gradients and illustrate how differences between ligand recognition and receptor activation influence the signaling machinery that drives cellular movement into and out of the tumor microenvironment. Facets of chemokine physiology across discrete cancer immune phenotypes are contrasted to existing chemokine-centered therapies in cancer.

Funder

HHS | NIH | National Cancer Institute

HHS | NIH | National Institute of General Medical Sciences

Children’s Research Institute, Children’s Hospital of Wisconsin

HHS | NIH | National Center for Advancing Translational Sciences

Hanis-Stepka-Rettig Endowed Chair in Cancer Research, Medical College of Wisconsin

Bobbie Nick Voss Charitable Foundation

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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