PMID- 28214198 OWN - NLM STAT- MEDLINE DCOM- 20170406 LR - 20220410 IS - 1618-0631 (Electronic) IS - 0344-0338 (Linking) VI - 213 IP - 3 DP - 2017 Mar TI - Tumor-derived CD4+CD25+regulatory T cells inhibit dendritic cells function by CTLA-4. PG - 245-249 LID - S0344-0338(16)30236-9 [pii] LID - 10.1016/j.prp.2016.12.008 [doi] AB - PURPOSE: CD4+CD25+regulatoryT cells (Tregs) play an important role in anti-tumor immune responses. Poor prognosis and declining survival rates have intimate connection with high Treg expression in cancer patients. Cytotoxic T Lymphocyte-associated protein (CTLA-4) is one of the most prominent molecules on Treg. In our previous research, we have demonstrated that HCC-derived Tregs can interfere with Dendritic cells (DCs) function and down-modulate CD80/CD86 on DCs in vitro in a cell-contact dependent way. However the mechanism of how HCC-derived Treg affect DC phenotype are not very clear. Therefore, we investigated the function of CTLA-4 in anti-tumor immune responses. MATERIALS AND METHODS: We established BABL/C mouse with hepatocellular carcinoma model, and tumor-derived Tregs were purified by magnetic cell sorting using mouse CD4+CD25+regulatoryT cell isolation kit. Splenic DCs were enriched using CD11c-conjugated microbeads. Then splenic DCs co-cultured with tumor-derived Tregs and antibody-blocking experiments was performed. RESULTS: In our research, we found the down-modulation of CD80/CD86 on DCs was inhibited by blocking CTLA-4. HCC-derived Tregs down-modulated CD80/CD86 on DCs in a CTLA-4-dependent way. Blockade of CTLA-4 can lead to increase DC-mediated immunity. CONCLUSION: CTLA-4 play a vital role in Treg-mediated immnue inhibition and this discovery can open up new ideas for the development of therapeutic strategies. CI - Copyright (c) 2016 Elsevier GmbH. All rights reserved. FAU - Chen, Xin AU - Chen X AD - Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. FAU - Du, Yong AU - Du Y AD - Department of Pediatrics, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, ZheJiang, China. FAU - Hu, Qingqing AU - Hu Q AD - Department of Pediatrics, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, ZheJiang, China. FAU - Huang, ZhiMing AU - Huang Z AD - Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. Electronic address: 515359290@qq.com. LA - eng PT - Journal Article DEP - 20161221 PL - Germany TA - Pathol Res Pract JT - Pathology, research and practice JID - 7806109 RN - 0 (CTLA-4 Antigen) SB - IM MH - Animals MH - CTLA-4 Antigen/*metabolism MH - Carcinoma, Hepatocellular/immunology/metabolism/pathology MH - Dendritic Cells/*metabolism MH - Liver Neoplasms/immunology/metabolism/pathology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - T-Lymphocytes, Regulatory/*metabolism OTO - NOTNLM OT - CD4+CD25+regulatory T cell OT - CTLA-4 OT - Dendritic cell EDAT- 2017/02/19 06:00 MHDA- 2017/04/07 06:00 CRDT- 2017/02/19 06:00 PHST- 2016/07/06 00:00 [received] PHST- 2016/10/16 00:00 [revised] PHST- 2016/12/15 00:00 [accepted] PHST- 2017/02/19 06:00 [pubmed] PHST- 2017/04/07 06:00 [medline] PHST- 2017/02/19 06:00 [entrez] AID - S0344-0338(16)30236-9 [pii] AID - 10.1016/j.prp.2016.12.008 [doi] PST - ppublish SO - Pathol Res Pract. 2017 Mar;213(3):245-249. doi: 10.1016/j.prp.2016.12.008. Epub 2016 Dec 21.