Lack of proper innate sensing inside tumor microenvironment (TME) limits T cell-targeted immunotherapy. NAD(P)H:quinone oxidoreductase 1 (NQO1) is highly enriched in multiple tumor types and has emerged as a promising target for direct tumor-killing. Here, we demonstrate that NQO1-targeting prodrug β-lapachone triggers tumor-selective innate sensing leading to T cell-dependent tumor control. β-Lapachone is catalyzed and bioactivated by NQO1 to generate ROS in NQO1 high tumor cells triggering oxidative stress and release of the damage signals for innate sensing. β-Lapachone-induced high mobility group box 1 (HMGB1) release activates the host TLR4/MyD88/type I interferon pathway and Batf3 dendritic cell-dependent cross-priming to bridge innate and adaptive immune responses against the tumor. Furthermore, targeting NQO1 is very potent to trigger innate sensing for T cell re-activation to overcome checkpoint blockade resistance in well-established tumors. Our study reveals that targeting NQO1 potently triggers innate sensing within TME that synergizes with immunotherapy to overcome adaptive resistance.

HighlightStrigolactones monitor lateral root development in a spatiotemporal manner by an interplay with cytokinin.

General strategies leading to scale-span molecular self-assembly are of crucial importance in creating bulk supramolecular materials. Here, we report that under mechanical pressure, caking of the precipitated molecular self-assemblies led to bulk supramolecular films. Massive fabrication of supramolecular films became possible by employing a simple household noodle machine. The film could be endowed to acquire diversified functions by depositing various functional ingredients via coprecipitation. We expect that our current work opens up a new paradigm leading to large-scale functional solid molecular self-assembled materials.