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Updated: Sep 9, 2026

Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
Published on: August 1, 2025
Dendritic cell centric nanoengineering couples antigen acquisition and STING activation for cancer immunotherapy
Shuting Xiang1, Shanshan Ma2, Tuzhi Xu1
1Department of Pharmaceutics, Jiang Su Key Laboratory of Drug Design and Optimization, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Abstract:
Stimulator of interferon genes (STING) agonists have shown limited antitumor efficacy, in part because STING activation is not preferentially focused on dendritic cells (DCs), which specialize in cross-priming. We present a DC-centric strategy that synergistically licenses DCs by coordinating CD47-SIRPα checkpoint relief and STING activation via dual ultra-pH-sensitive gating. Mild tumor acidity first unmasks the αCD47 cue to prime antigen acquisition. Following DC-biased uptake, a second acidic gate releases cGAMP to engage STING in antigen-bearing DCs. Functionally, efficacy requires Batf3-dependent cDC1s and CD8+ T cells, yet is preserved after macrophage depletion. In murine models, this strategy suppresses tumor growth and metastasis with good tolerability, and it retains activity in a humanized cell-line-derived xenograft model established in NSG-SGM3 hosts, supporting activity in a partially reconstituted human immune setting. Together, this work presents a mechanism-guided combination strategy to optimize STING agonist therapy.
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