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Viral mimicry may help explain immunogenic cell death.

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Proceedings of the National Academy of Sciences of the United States of America 📖 저널 OA 100% 2022: 2/2 OA 2023: 1/1 OA 2024: 8/8 OA 2025: 44/44 OA 2026: 58/58 OA 2022~2026 2026 Vol.123(11) p. e2537547123 OA
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Levine MS, Li J, Ehrlich LIR, DePinho RA, Iverson B, Sessler JL

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Viral mimicry may be an underappreciated contributor to chemotherapeutic potency in animal models and patients.

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APA Levine MS, Li J, et al. (2026). Viral mimicry may help explain immunogenic cell death.. Proceedings of the National Academy of Sciences of the United States of America, 123(11), e2537547123. https://doi.org/10.1073/pnas.2537547123
MLA Levine MS, et al.. "Viral mimicry may help explain immunogenic cell death.." Proceedings of the National Academy of Sciences of the United States of America, vol. 123, no. 11, 2026, pp. e2537547123.
PMID 41811449 ↗

Abstract

Viral mimicry may be an underappreciated contributor to chemotherapeutic potency in animal models and patients. This hypothesis is based on studies of a bis-Au(I)-NHC complex that was found to generate a strong in vivo in two different challenge studies using an iKAP colorectal cancer mouse model. RNA profiling of treated cells revealed the stimulation of genes that overlap with those upregulated during a viral infection. The bis-Au(I)-NHC complex generates reactive oxygen species (ROS) through the simultaneous redox cycling of the naphthoquinone moiety and inhibition of thioredoxin reductase with Au(I). This ROS increase causes endoplasmic reticulum stress, activation of the unfolded protein response pathway and upregulation of Ifih1, a gene that encodes for the viral dsRNA sensor MDA5. Activation of MDA5 triggers a strong type I interferon response and expression of chemokine ligand 10 that can recruit immune cells to the treated tumor in a manner analogous to immune responses during viral infection. This proposed mechanism bridges the gap between cytotoxicity and the innate and adaptive immune responses. We suggest viral mimicry may be a key driver of chemotherapy potency in animals and an important determinant of positive outcomes in cancer patients.

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