RGD Reference Report - Low-dose splenic radiation inhibits liver tumor development of rats through functional changes in CD4+CD25+Treg cells. - Rat Genome Database

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Low-dose splenic radiation inhibits liver tumor development of rats through functional changes in CD4+CD25+Treg cells.

Authors: Wang, B  Li, B  Dai, Z  Ren, S  Bai, M  Wang, Z  Li, Z  Lin, S  Wang, Z  Huang, N  Yang, P  Liu, M  Min, W  Ma, H 
Citation: Wang B, etal., Int J Biochem Cell Biol. 2014 Oct;55:98-108. doi: 10.1016/j.biocel.2014.08.014. Epub 2014 Aug 25.
RGD ID: 11049493
Pubmed: PMID:25168696   (View Abstract at PubMed)
DOI: DOI:10.1016/j.biocel.2014.08.014   (Journal Full-text)

The increased number of CD4(+)CD25(+)Treg cells in tumor local and peripheral splenic tissues is related to the low immune function as well as to tumor recurrence and metastasis. Our pre-clinical studies showed that low-dose radiation (LDR) of the spleen in liver cancer patients significantly improves immune functions. However, the molecular mechanisms of such radiation remained ill defined. This study explores the role of CD4(+)CD25(+)Treg cells in radiation-induced immunomodulatory effects. Using the diethylnitrosamine (DEN)-induced rat liver tumor model and in vitro cell experiments, the percentage of CD4(+)CD25(+)Treg/CD4(+) cells in the blood and the expressions of Foxp3(+), IL-10, TGF-beta, and cytotoxic T lymphocyte-associated antigen-4(CTLA-4) in spleen and liver tumors significantly decreased after LDR of the spleen in rats with liver cancer. The tumors became smaller than those in the non-radiated group, with both showing a parallel relation. Flow cytometry and MTT results revealed that LDR failed to inhibit CD4(+)CD25(+)Treg cell proliferation. Conversely, apoptosis was reduced and proliferation was stimulated. This process also changed CTLA-4 molecule expression on the surfaces of CD4(+)CD25(+)Treg cells and reduced their inhibitory function against CD4(+)CD25(-)T cell proliferation, and the suppression function of CD4(+)CD25(+)Treg cells was further weakened with the introduction of the CTLA-4 inhibitor. Findings demonstrate that the reduction of CTLA-4 expression on the CD4(+)CD25(+)Treg cell surface and the further inhibition of cell function may be considered as important regulators of LDR-induced immunomodulatory effects. This study provides experimental evidence to elucidate the immune enhancement induced by this process and presents a novel method for liver cancer immunotherapy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
liver benign neoplasm treatmentISOIl10 (Rattus norvegicus)11049493; 11049493 RGD 
liver benign neoplasm treatmentIEP 11049493 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il10  (interleukin 10)

Genes (Mus musculus)
Il10  (interleukin 10)

Genes (Homo sapiens)
IL10  (interleukin 10)


Additional Information