biostudies-literatureUnknown60Zhang W<h4>Background</h4>We recently reported a novel IgG4-centered immune evasion mechanism in cancer, and this was achieved mostly through the Fc-Fc reaction of increased IgG4 to cancer-bound IgG in cancer microenvironment. The mechanism was suggested to be related to cancer hyperprogressive disease (HPD) which is a side-effect often associated to IgG4 subtype PD-1 antibody immunotherapy. HPD was reported to occur in cancers with certain mutated genes including KRAS and such mutations are often associated to glutathione (GSH) synthesis. Therefore, we hypothesize that IgG4 and GSH may play a synergistic role in local immunosuppression of cancer.<h4>Methods</h4>Quantitatively analyzed the distribution and abundance of GSH and IgG4 in human cancer samples with ELISA and immunohistochemistry. The Redox biology102608https://www.ebi.ac.uk/biostudies/studies/S-EPMC9868885biostudies-literatureSynergistic effect of glutathione and IgG4 in immune evasion and the implication for cancer immunotherapy.PMC9868885Hong LLi JZhao CZeng LChen MXu QMa XSu MLi PTian DWang HYan XZhang WFang ZZhu XGeng YGu JChen XChen SQuan YfalseSynergistic effect of glutathione and IgG4 in immune evasion and the implication for cancer immunotherapy.<h4>Background</h4>We recently reported a novel IgG4-centered immune evasion mechanism in cancer, and this was achieved mostly through the Fc-Fc reaction of increased IgG4 to cancer-bound IgG in cancer microenvironment. The mechanism was suggested to be related to cancer hyperprogressive disease (HPD) which is a side-effect often associated to IgG4 subtype PD-1 antibody immunotherapy. HPD was reported to occur in cancers with certain mutated genes including KRAS and such mutations are often associated to glutathione (GSH) synthesis. Therefore, we hypothesize that IgG4 and GSH may play a synergistic role in local immunosuppression of cancer.<h4>Methods</h4>Quantitatively analyzed the distribution and abundance of GSH and IgG4 in human cancer samples with ELISA and immunohistochemistry. The 2023-01-01T00:00:00Z2023 Apr2026-05-28T03:53:01.394Z2024-11-21T05:39:25.131ZS-EPMC98688853668104710.1016/j.redox.2023.102608