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Tumor-infiltrating regulatory T cells delineated by upregulation of PD-1 and inhibitory receptors.

Authors
 Hyo Jin Park  ;  Anthony Kusnadi  ;  Eun-Jung Lee  ;  Won Woo Kim  ;  Byoung Chul Cho  ;  Ik Jae Lee  ;  Jinsil Seong  ;  Sang-Jun Ha 
Citation
 Cellular Immunology, Vol.278(1-2) : 76-83, 2012 
Journal Title
 Cellular Immunology 
ISSN
 0008-8749 
Issue Date
2012
Keywords
TILs ; Tumor-infiltrating Treg cells ; PD-1 ; Inhibitory receptors
Abstract
Foxp3(+) regulatory T (T(reg)) cells are dominant suppressor cells which regulate conventional T (T(conv)) cells. Inside tumor microenvironment, T(reg) cells have been known to become potent in suppressing T(conv) cell responses, thereby enabling tumor cells to circumvent immune response. However, the underlying mechanism by which tumor-infiltrating T(reg) cells display enhanced suppressive function is still unresolved. To understand characteristics and function of tumor-infiltrating T(reg) cells as well as T(conv) cells in the tumor site, we analyzed their phenotypes either within tumor burden or at distant site of tumor using both heterotopic and orthotopic mouse cancer models. Compared to CD8(+) T cells at distant site of tumor, tumor-infiltrating CD8(+) T cells dramatically upregulated programmed death 1 (PD-1) and other inhibitory receptors, thereby being more exhausted functionally. Tumor-infiltrating CD4(+) T cells also expressed higher level of PD-1 than CD4(+) T cells at distant site of tumor but very surprisingly, upregulation of PD-1 occurred in CD4(+)Foxp3(+) T(reg) as well as CD4(+)Foxp3(-) T(conv) cells. Moreover, tumor infiltrating T(reg) cells upregulated other inhibitory receptors such as T cell immunoglobulin mucin 3 (TIM-3), cytotoxic T lymphocyte antigen-4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and lymphocyte activation gene-3 (LAG-3). These results suggest that upregulation of PD-1 and other inhibitory receptors on tumor-infiltrating T(reg) cells is related with their enhanced suppressive function.
Full Text
http://www.sciencedirect.com/science/article/pii/S0008874912001384
DOI
10.1016/j.cellimm.2012.07.001
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
Yonsei Authors
Kim, Won Woo(김원우)
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
Lee, Eun Jung(이은정)
Lee, Ik Jae(이익재) ORCID logo https://orcid.org/0000-0001-7165-3373
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89918
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