Ccl22 diverts T regulatory cells and controls the growth of melanoma

Jared Klarquist, Kristen Tobin, Peyman Farhangi Oskuei, Steven W. Henning, Manuel F. Fernandez, Emilia R. Dellacecca, Flor C. Navarro, Jonathan M. Eby, Shilpak Chatterjee, Shikhar Mehrotra, Joseph I. Clark, I. Caroline Le Poole*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

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 an approximately two-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.

Original languageEnglish (US)
Pages (from-to)6230-6240
Number of pages11
JournalCancer Research
Volume76
Issue number21
DOIs
StatePublished - Nov 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Klarquist, J., Tobin, K., Oskuei, P. F., 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. (2016). Ccl22 diverts T regulatory cells and controls the growth of melanoma. Cancer Research, 76(21), 6230-6240. https://doi.org/10.1158/0008-5472.CAN-16-0618