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Ccl22 Diverts T Regulatory Cells and Controls the Growth of Melanoma
Cancer research (Chicago, Ill.), 2016-11, Vol.76 (21), p.6230-6240
Klarquist, Jared
Tobin, Kristen
Farhangi Oskuei, Peyman
Henning, Steven W
Fernandez, Manuel F
Dellacecca, Emilia R
Navarro, Flor C
Eby, Jonathan M
Chatterjee, Shilpak
Mehrotra, Shikhar
Clark, Joseph I
Le Poole, I Caroline
2016
Details
Autor(en) / Beteiligte
Klarquist, Jared
Tobin, Kristen
Farhangi Oskuei, Peyman
Henning, Steven W
Fernandez, Manuel F
Dellacecca, Emilia R
Navarro, Flor C
Eby, Jonathan M
Chatterjee, Shilpak
Mehrotra, Shikhar
Clark, Joseph I
Le Poole, I Caroline
Titel
Ccl22 Diverts T Regulatory Cells and Controls the Growth of Melanoma
Ist Teil von
Cancer research (Chicago, Ill.), 2016-11, Vol.76 (21), p.6230-6240
Ort / Verlag
United States
Erscheinungsjahr
2016
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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.
Sprache
Englisch
Identifikatoren
ISSN: 0008-5472
eISSN: 1538-7445
DOI: 10.1158/0008-5472.CAN-16-0618
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5242486
Format
–
Schlagworte
Animals
,
Cell Proliferation
,
Chemokine CCL22 - physiology
,
Humans
,
Melanoma - pathology
,
Melanoma - therapy
,
Mice
,
Mice, Inbred C57BL
,
Receptors, CCR4 - physiology
,
Skin - immunology
,
T-Lymphocytes, Regulatory - physiology
,
Vaccination
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