Physiology of chemokines in the cancer microenvironment. Am J Physiol Cell Physiol 2023 Jan 01;324(1):C167-C182
Date
11/02/2022Pubmed ID
36317799Pubmed Central ID
PMC9829481DOI
10.1152/ajpcell.00151.2022Scopus ID
2-s2.0-85145954846 (requires institutional sign-in at Scopus site) 1 CitationAbstract
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.
Author List
Drouillard D, Craig BT, Dwinell MBAuthors
Brian T. Craig MD Assistant Professor in the Surgery department at Medical College of WisconsinMichael B. Dwinell PhD Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
ChemokinesHumans
Ligands
Neoplasms
Precision Medicine
Tumor Microenvironment
