Journal
ONCOIMMUNOLOGY
Volume 5, Issue 4, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2015.1102828
Keywords
FOXP3; plasticity; RORt; regulatory T Cells; suppression; surface Markers; Th2 cell; Th17 cell
Categories
Funding
- Research Council of Norway [221938, 204784, 187615]
- Norwegian Cancer Society [741746, 419544]
- KG Jebsen Foundation [2012/21, 2012/23]
- South Eastern Norway Regional Health Authority [2010038]
Ask authors/readers for more resources
Pancreatic ductal adenocarcinoma (PDAC) is highly infiltrated by CD4(+)T cells that express RORt and IL-17 (T(H)17). Compelling evidence from the tumor microenvironment suggest that regulatory T cells (T-reg) contribute to T(H)17 mediated inflammation. Concurrently, PDAC patients have elevated levels of pro-inflammatory cytokines that may lead to T(H)17 associated functional plasticity in T-reg. In this study, we investigated the phenotype and functional properties of T-reg in patients with PDAC. We report that PDAC patients have elevated frequency of FOXP3(+)T(reg), which exclusively occurred within the FOXP3(+)RORt(+)T(reg) compartment. The FOXP3(+)RORt(+)T(reg) retained FOXP3(+)T(reg) markers and represented an activated subset. The expression of RORt in T-reg may indicate a phenotypic switch toward T(H)17 cells. However, the FOXP3(+)RORt(+)T(reg) produced both T(H)17 and T(H)2 associated pro-inflammatory cytokines, which corresponded with elevated T(H)17 and T(H)2 immune responses in PDAC patients. Both the FOXP3(+)T(reg) and FOXP3(+)RORt(+)T(reg) from PDAC patients strongly suppressed T cell immune responses, but they had impaired anti-inflammatory properties. We conclude that FOXP3(+)RORt(+)T(reg) have a dual phenotype with combined pro-inflammatory and immunosuppressive activity, which may be involved in the pathogenesis of PDAC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available