Boosting immunotherapy efficacy: Empowering the Potency of Dendritic cells loaded with breast cancer lysates through CTLA-4 suppression

Abstract

Anticancer immunotherapies with a dendritic Cell (DC) basis are becoming more popular. However, it has been suggested that the tumor's immunosuppressive mechanisms, such as inhibitory immunological checkpoint molecules, reduce the effectiveness of anticancer immunogenicity mediated by DC. Thus, overcoming immune checkpoints and inducing effective antigen-specific T-cell responses uniquely produced with malignant cells represent the key challenges. Among the inhibitory immune checkpoints, DCs' ability to mature and present antigens is decreased by CTLA-4 expression. Consequently, we hypothesized that by expressing CTLA-4 cells on DCs, the T cells' activation against tumor antigens would be suppressed when confronted with these antigens presented by DCs. In this research, by loading cell lysate of breast cancer (BC) on DCs and the other hand by inhibiting the induction of CTLA-4 using small interfering RNA (siRNA), we assessed the functional activities and phenotypes of DCs, and also the responses associated with T-cells following co-culture DC/T cell. Our research has shown that the suppression of CTLA-4 enhanced the stimulating capabilities of DCs. Additionally, CTLA-4-suppressed BC cell lysate-loaded DCs produced more IL-4 and IFN-ϒ and increased T cell induction in contrast to DCs without CTLA-4 suppression. Together, our data point to CTLA-4-suppressed DCs loaded with BC cell lysate as a potentially effective treatment method. However, further research is required before employing this method in therapeutic contexts.

Keywords

• Dendritic cell
• Immune checkponits
• CTLA-4
• Breast cancer
• SiRNA
• Cancer immunotherapy