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 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. Cancer Res; 76(21); 6230-40. ©2016 AACR.
authors.affiliation: Oncology Research Institute, Loyola University Chicago, Maywood, Illinois.
authors.forename: Jared
authors.initials: J
authors.lastname: Klarquist
authors.affiliation: Department of Medicine, Loyola University Chicago, Maywood, Illinois.
authors.forename: Kristen
authors.initials: K
authors.lastname: Tobin
authors.affiliation: Oncology Research Institute, Loyola University Chicago, Maywood, Illinois.
authors.forename: Peyman
authors.initials: P
authors.lastname: Farhangi Oskuei
authors.affiliation: Oncology Research Institute, Loyola University Chicago, Maywood, Illinois.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Henning
authors.affiliation: Oncology Research Institute, Loyola University Chicago, Maywood, Illinois.
authors.forename: Manuel F
authors.initials: MF
authors.lastname: Fernandez
authors.affiliation: Oncology Research Institute, Loyola University Chicago, Maywood, Illinois.
authors.forename: Emilia R
authors.initials: ER
authors.lastname: Dellacecca
authors.affiliation: Oncology Research Institute, Loyola University Chicago, Maywood, Illinois.
authors.forename: Flor C
authors.initials: FC
authors.lastname: Navarro
authors.affiliation: Oncology Research Institute, Loyola University Chicago, Maywood, Illinois.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Eby
authors.affiliation: Department of Surgery/Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Shilpak
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Department of Surgery/Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Shikhar
authors.initials: S
authors.lastname: Mehrotra
authors.affiliation: Oncology Research Institute, Loyola University Chicago, Maywood, Illinois.|Department of Medicine, Loyola University Chicago, Maywood, Illinois.
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.affiliation: Oncology Research Institute, Loyola University Chicago, Maywood, Illinois. ilepool@luc.edu.|Departments of Pathology, Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois.
authors.forename: I Caroline
authors.initials: IC
authors.lastname: Le Poole
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D054422:Chemokine CCL22 / Q000502:physiology*; D006801:Humans; D008545:Melanoma / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D054398:Receptors, CCR4 / Q000502:physiology; D012867:Skin / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D014611:Vaccination
chemical_list: C515482:CCL22 protein, human; C515354:CCR4 protein, human; D054422:Chemokine CCL22; D054398:Receptors, CCR4