TLR7 诱导单核细胞衍生树突状细胞产生线粒体活性氧，驱动 IL-12 依赖性 NK 细胞活化并增强抗肿瘤免疫

Dendritic cell (DC)-based vaccines are promising immunotherapies for cancer. Although DC-based therapies are known to activate tumor-specific T cells, the interplay between DCs and NK cells in this setting is not fully understood. In this study, we demonstrated a novel TLR7/ mitochondrial reactive oxygen species (mROS)/IL-12 axis that drives potent NK cell responses against tumors.

We showed that TLR7 activation by imiquimod in peripheral blood monocyte-derived CD11c+ DCs triggered mROS production, leading to enhanced IL-12 secretion and subsequent NK cell activation, as evidenced by increased IFN-γ production and tumor cell cytotoxicity.

Notably, mROS neutralization abrogates NK cell-mediated tumor cell lysis, and TLR7-mediated DC activation of NK cells occurs independently of MyD88, suggesting involvement of the noncanonical NF-κB pathway.

Our findings provide a rationale for targeting the TLR7/mROS/IL-12 axis to enhance the efficacy of DC-based cancer immunotherapy.