Exploring Clec9a in dendritic cell-based tumor immunotherapy for molecular insights and therapeutic potentials

作者：Zubair Hussain, Yueteng Zhang, Lu Qiu, Shanshan Gou, Kangdong Liu · 发表于：npj Vaccines · 年份：2025 · DOI：10.1038/s41541-025-01084-2 · 被引用次数：19 · 研究领域：Immunotherapy and Immune Responses、RNA Interference and Gene Delivery、vaccines and immunoinformatics approaches

The pivotal role of type 1 conventional dendritic cells (cDC1s) in the field of dendritic cell (DC)-based tumor immunotherapies has been gaining increasing recognition due to their superior antigen cross-presentation abilities and essential role in modulating immune responses. This review specifically highlights the C-type lectin receptor family 9 member A (Clec9a or DNGR-1), which is exclusively expressed on cDC1s and plays a pivotal role in augmenting antigen cross-presentation and cytotoxic T lymphocyte (CTL) responses while simultaneously mitigating off-target effects. These effects include the enhancement of the cDC1s cross-presentation, reducing autoimmune responses and systemic inflammation, as well as preventing the non-specific activation of other immune cells. Consequently, these actions may contribute to reduced toxicity and enhanced treatment efficacy in immunotherapy. The exceptional ability of Clec9a to cross-present dead cell-associated antigens and enhance both humoral and CTL responses makes it an optimal receptor for DC-based strategies aimed at strengthening antitumor immunity. This review provides a comprehensive overview of the molecular characterization, expression, and signaling mechanisms of Clec9a. Furthermore, it discusses the role of Clec9a in the induction and functional activation of Clec9a + cDC1s, with a particular focus on addressing the challenges related to off-target effects and immune tolerance in the development of tumor vaccines. Addition...