ArticleJournal for immunotherapy of cancer2026
Targeting GRP75 by natural compound polyphyllin II triggers mitochondrial calcium overload and pyroptosis to potentiate cancer immunotherapy.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundImmune checkpoint blockade (ICB) therapy has emerged as a pivotal cancer treatment by activating antitumor immunity. However, its clinical efficacy remains limited in many patients, highlighting the need for combination strategies to overcome resistance. Inducing immunogenic cell death (ICD) represents a promising approach to remodel the immunosuppressive tumor microenvironment and improve ICB efficacy.
methodsA high-throughput screen of a natural compound library identified potent ICD inducers. Polyphyllin II (PPII), a bioactive component from
resultsPPII was identified as a potent ICD inducer, stimulating the release of high mobility group box 1, ATP, and calreticulin from tumor cells. PPII suppressed tumor growth and enhanced antitumor immunity by promoting dendritic cell maturation and antigen cross-presentation, leading to CD8
conclusionOur findings identify GRP75 as a novel therapeutic target for cancer immunotherapy and highlight PPII-driven immune reprogramming as a translatable strategy to potentiate ICB efficacy through the induction of immunogenic pyroptosis.
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