1. CCR4 Antagonists Inhibit Treg Trafficking into the Tumor Microenvironment
- Author
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John M. Ketcham, Lisa A. Marshall, and Oezcan Talay
- Subjects
0301 basic medicine ,Tumor microenvironment ,Chemokine ,biology ,Chemistry ,Organic Chemistry ,CCR4 ,FOXP3 ,hemic and immune systems ,chemical and pharmacologic phenomena ,Biochemistry ,Small molecule ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Drug Discovery ,Cancer research ,biology.protein ,CCL17 ,sense organs ,IL-2 receptor ,CCL22 - Abstract
Recruitment of naturally occurring suppressive CD4+, CD25+, and FOXP3+ regulatory T cells (Treg) to the tumor microenvironment (TME) has the potential to weaken the antitumor response in patients receiving treatment with immuno-oncology (IO) agents. Human Treg express CCR4 and can be recruited to the TME through the C-C chemokines CCL17 and CCL22. We have recently developed a series of potent, orally bioavailable small molecule antagonists of CCR4 that can block recruitment of Treg into the TME.
- Published
- 2018
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