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

Authors
 Hyo Jin Park ; Anthony Kusnadi ; Sang-Jun Ha ; Jinsil Seong ; Ik Jae Lee ; Byoung Chul Cho ; Won Woo Kim ; Eun-Jung Lee 
Citation
 Cellular Immunology, Vol.278(1-2) : 76~83, 2012 
Journal Title
 Cellular Immunology 
ISSN
 0008-8749 
Issue Date
2012
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/89918
DOI
10.1016/j.cellimm.2012.07.001
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Radiation Oncology
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Medical Research Center
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S0008874912001384
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