mRNA and the toll-like receptor 7/8 (TLR7/8) agonist 3M-052. The goal is to establish a cancer immunity cycle by promoting endogenous tumor antigen release by the generation of KRAS-specific cytotoxic T cells. Using an orthotopic PDAC mouse model, it is demonstrated that this dual-platform approach significantly reduces tumor burden and extends survival compared to monotherapies. Bulk RNA sequencing and gene expression analyses further reveal synergy between the immune responses at the primary tumor site and the spleen, including maximal upregulation of apoptosis-related genes, endoplasmic reticulum stress pathways, antigen presentation pathways, and T cell activation markers. These findings indicate that the combinatorial strategy effectively bridges innate and adaptive immunity. In conclusion, this study highlights the potential of nanocarrier-based immunotherapy to enhance PDAC immunity by integrating ICD induction with systemic immune reprogramming, offering a promising avenue for improving treatment outcomes.
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Luo et al. (2025) studied this question.