چاپ صفحه |  صفحه نخست سامانه |  چکیده مقاله |  نویسندگان |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| Dendritic cell (DC)-based cancer immunotherapy is one of the most important anti-cancer immunotherapies, which has been associated with variable efficiencies in different cancer types. It is well-known that tumor microenvironment plays a key role in the efficacy of various immunotherapies such as DC vaccine. Accordingly, the expression of PD-L1 on DCs, which interacts with PD-1 on T cells leads to inhibition of anti-tumor responses following presentation of tumor antigens by DCs to T cells. Therefore, we hypothesized that downregulation of PD-L1 in DCs in association with silencing of PD-1 on T cells may lead to enhancement of T cell priming by DCs to have efficient anti-tumor T cell responses. In this study, we silenced the expression of PD-L1 in DCs and PD-1 in T cells by siRNA-loaded chitosan-dextran sulfate nanoparticles (NPs) and evaluated the DC phenotypic and functional characteristics and T cells functions following tumor antigen recognition on DCs, ex vivo. Our results showed that synthesized NPs had good physicochemical characteristics (size of 77.5 nm and zeta potential of 14.3) that was associated with efficient cellular uptake and target gene silencing. Moreover, PD-L1 silencing was associated with stimulatory characteristics of DCs. On the other hand, presentation of tumor antigens by PD-L1 negative DCs to PD-1-silenced T cells led to induction of potent T-cell responses. Our findings imply that PD-L1-silenced DCs can be considered as a potent immunotherapeutic approach in combination with PD-1-siRNA loaded NPs, however; further in vivo investigation is required in animal models. |
| نویسنده | نفر چندم مقاله |
|---|---|
| هادی حسن نیا | اول |
| مهدی یوسفی | سیزدهم |
| فرهاد جدیدی نیارق | چهاردهم |
| میترا قاسمی چالشتری | دوم |
| علی مسجدی | پنجم |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| Blockage of immune checkpoint molecules increases T cel priming potential of dendritic cell vaccine.pdf | 1398/09/20 | 4670844 | دانلود |
