Ccl22 Diverts T Regulatory Cells and Controls the Growth of Melanoma Journal Article


Authors: Klarquist, J.; Tobin, K.; Farhangi Oskuei, P.; Henning, S. W.; Fernandez, M. F.; Dellacecca, E. R.; Navarro, F. C.; Eby, J. M.; Chatterjee, S; Mehrotra, S; Clark, J. I.; Le Poole, I. C.
Article Title: Ccl22 Diverts T Regulatory Cells and Controls the Growth of Melanoma
Abstract: T regulatory cells (Treg) avert autoimmunity but their increased levels in melanoma confer a poor prognosis. To explore the basis for Treg accumulation in melanoma, we evaluated chemokine expression in patients. A 5-fold increase was documented in the Treg chemoattractants CCL22 and CCL1 in melanoma-affected skin versus unaffected skin, as accompanied by infiltrating FoxP3+ T cells. In parallel, there was a ~2-fold enhancement in expression of CCR4 in circulating Treg but not T effector cells. We hypothesized that redirecting Treg away from tumors might suppress autoimmune side-effects caused by immune checkpoint therapeutics now used widely in the clinic. In assessing this hypothesis, we observed a marked increase in skin Treg in mice vaccinated with CCL22, with repetitive vaccination sufficient to limit Treg accumulation and melanoma growth in the lungs of animals challenged by tumor cell injection, whether using a prevention or treatment protocol design. The observed change in Treg accumulation in this setting could not be explained by Treg conversion. Overall, our findings offered a preclinical proof of concept for the potential use of CCL22 delivered by local injection as a strategy to enhance the efficacious response to immune checkpoint therapy while suppressing its autoimmune side-effects.
Journal Title: Cancer research
ISSN: 1538-7445; 0008-5472
Publisher: American Association for Cancer Research  
Journal Place: United States
Date Published: 2016
Language: ENG
DOI/URL:
Notes: LR: 20161019; CI: Copyright {copyright, serif}2016; GR: T35 HL120835/HL/NHLBI NIH HHS/United States; JID: 2984705R; 2016/08/30 [accepted]; 2016/03/01 [received]; aheadofprint