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Toll-like receptor 7/8 (TLR-7/8) agonists serve as a promising class of pattern recognition receptors that effectively evoke the innate immune response, making them promising immunomodulatory agents for tumor immunotherapy. However, the uncontrollable administration of TLR-7/8 agonists frequently leads to the occurrence of severe immune-related adverse events (irAEs). Thus, it is imperative to strategically design tumor-microenvironment-associated biomarkers or exogenous stimuli responsive TLR-7/8 agonists in order to accurately evaluate and activate innate immune responses. No comprehensive elucidation has been documented thus far regarding TLR-7/8 immune agonists that are specifically engineered to enhance immune activation. In this feature article, we provide an overview of the advancements in TLR-7/8 agonists, aiming to enhance the comprehension of their mechanisms and promote the clinical progression through nanomedicine strategies. The current challenges and future directions of cancer immunotherapy are also discussed, with the hope that this work will inspire researchers to explore innovative applications for triggering immune responses through TLR-7/8 agonists. [ABSTRACT FROM AUTHOR]

An NQO1-responsive precursor, named R848-QPA, has been developed to evoke an anti-tumor immune response. R848-QPA can induce innate immune activation when activated by overexpressed NQO1 in the tumor microenvironment while showing lower activity in NQO1-deprived environments. This strategy provides a new method for the development of tumor-microenvironment-responsive prodrugs for antitumor immunotherapy. [ABSTRACT FROM AUTHOR]