1204 Immunogenic cell death by inhibition of glucose-6-phosphate dehydrogenase enhances the efficacy of immunotherapy in malignant melanoma
نویسندگان
چکیده
Immunogenic cell death (ICD) is accompanied by changes in the composition of surface and release soluble mediators. Such signals operate on dendritic cells to stimulate presentation tumor antigens T cells. We recently found that low expression glucose-6-phosphate dehydrogenase (G6PD), a cytoplasmic enzyme involved pentose phosphate pathway, correlates with active anti-tumor immunity. G6PD maintains NADPH levels protects from oxidative damage. The present study demonstrates inhibition induces ICD as mechanism for activating immunity, intending develop combination treatment malignant melanoma. Chemical or genetic increased hydrogen peroxide-induced releasing high mobility group box 1 (HMGB1). Immunocytochemistry revealed calreticulin migrated dying Comprehensive gene analysis 83 melanoma samples NCBI GEO database showed causes upregulation endoplasmic reticulum stress-related genes. These findings indicate immunogenic death. next investigated efficacy therapy involving blockade anti-PD-1 antibody administration using mouse model. C57BL/6 mice transplanted G6PD-knockout B16 treated significant reduction size. In clinical settings, among 42 patients immune checkpoint inhibitors, those had better prognosis than (p=0.0473). not only promising biomarker but also new therapeutic target. Inhibition tumors death, which increases antigen presentation, thereby increasing effects inhibitors.
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2023
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2023.03.1218