Tumor-derived CD4+CD25+regulatory T cells inhibit dendritic cells function by CTLA-4.

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.