{"title":"STAT3抑制剂与赫赛汀联合降低免疫检查点表达并激发抗乳腺癌免疫:一项体外研究","authors":"Amirhossein Jahangiri, Rana Ezzeddini, Nazanin Zounemat Kermani, Fariborz Bahrami, Amir Salek Farrokhi","doi":"10.1111/sji.13300","DOIUrl":null,"url":null,"abstract":"<p><p>Breast cancer (BC) is the most prevalent diagnosed cancer among women. Herceptin blocks the effects of Her-2 and tumour cell growth. Despite many achievements using Herceptin in Her-2<sup>+</sup> invasive BC treatment, there are treatment failures and resistances. The signal transducer and activator of transcription 3 (STAT3) is persistently activated in BC and is associated with immune suppression and tumour cell proliferation. We evaluated whether STAT3 inhibition could increase Herceptin impact on in vitro reduction of immune checkpoint inhibitors and polarize T cells to a protective immune response. We treated SK-BR-3 cells with Herceptin and the STAT3-inhibitor (FLLL32) and assessed the apoptosis and expression of apoptosis-related proteins, VEGF, Her-2 and apoptosis targets of STAT3. PBMCs were isolated from healthy donors and co-cultured with SK-BR-3 cells in the presence or absence of Herceptin and FLLL32. PD-L1, CTLA-4, TIM-3 and T-cell intracellular cytokines were then evaluated. Our results demonstrated that STAT3 inhibition and Herceptin increased SK-BR-3 cell apoptosis, significantly. STAT3 inhibition through combination treatment had a more significant effect on regulating PD-1, TIM-3 and CTLA-4 expression on PBMCs. Alternatively, the combination of FLLL32 and Herceptin promoted T helper-1 protective immune response. The combination of FLLL32 and Herceptin suppress the expression of immune checkpoints and provoke the T-helper1 immune response in lymphocytes. Our analysis indicates STAT3 as a promising target that improves Herceptin's role in breast cancer cell apoptosis.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Combination of STAT3 inhibitor with Herceptin reduced immune checkpoints expression and provoked anti-breast cancer immunity: An in vitro study.\",\"authors\":\"Amirhossein Jahangiri, Rana Ezzeddini, Nazanin Zounemat Kermani, Fariborz Bahrami, Amir Salek Farrokhi\",\"doi\":\"10.1111/sji.13300\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Breast cancer (BC) is the most prevalent diagnosed cancer among women. Herceptin blocks the effects of Her-2 and tumour cell growth. Despite many achievements using Herceptin in Her-2<sup>+</sup> invasive BC treatment, there are treatment failures and resistances. The signal transducer and activator of transcription 3 (STAT3) is persistently activated in BC and is associated with immune suppression and tumour cell proliferation. We evaluated whether STAT3 inhibition could increase Herceptin impact on in vitro reduction of immune checkpoint inhibitors and polarize T cells to a protective immune response. We treated SK-BR-3 cells with Herceptin and the STAT3-inhibitor (FLLL32) and assessed the apoptosis and expression of apoptosis-related proteins, VEGF, Her-2 and apoptosis targets of STAT3. PBMCs were isolated from healthy donors and co-cultured with SK-BR-3 cells in the presence or absence of Herceptin and FLLL32. PD-L1, CTLA-4, TIM-3 and T-cell intracellular cytokines were then evaluated. Our results demonstrated that STAT3 inhibition and Herceptin increased SK-BR-3 cell apoptosis, significantly. STAT3 inhibition through combination treatment had a more significant effect on regulating PD-1, TIM-3 and CTLA-4 expression on PBMCs. Alternatively, the combination of FLLL32 and Herceptin promoted T helper-1 protective immune response. The combination of FLLL32 and Herceptin suppress the expression of immune checkpoints and provoke the T-helper1 immune response in lymphocytes. Our analysis indicates STAT3 as a promising target that improves Herceptin's role in breast cancer cell apoptosis.</p>\",\"PeriodicalId\":21493,\"journal\":{\"name\":\"Scandinavian Journal of Immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2023-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Scandinavian Journal of Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/sji.13300\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/5/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scandinavian Journal of Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/sji.13300","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/5/24 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Combination of STAT3 inhibitor with Herceptin reduced immune checkpoints expression and provoked anti-breast cancer immunity: An in vitro study.
Breast cancer (BC) is the most prevalent diagnosed cancer among women. Herceptin blocks the effects of Her-2 and tumour cell growth. Despite many achievements using Herceptin in Her-2+ invasive BC treatment, there are treatment failures and resistances. The signal transducer and activator of transcription 3 (STAT3) is persistently activated in BC and is associated with immune suppression and tumour cell proliferation. We evaluated whether STAT3 inhibition could increase Herceptin impact on in vitro reduction of immune checkpoint inhibitors and polarize T cells to a protective immune response. We treated SK-BR-3 cells with Herceptin and the STAT3-inhibitor (FLLL32) and assessed the apoptosis and expression of apoptosis-related proteins, VEGF, Her-2 and apoptosis targets of STAT3. PBMCs were isolated from healthy donors and co-cultured with SK-BR-3 cells in the presence or absence of Herceptin and FLLL32. PD-L1, CTLA-4, TIM-3 and T-cell intracellular cytokines were then evaluated. Our results demonstrated that STAT3 inhibition and Herceptin increased SK-BR-3 cell apoptosis, significantly. STAT3 inhibition through combination treatment had a more significant effect on regulating PD-1, TIM-3 and CTLA-4 expression on PBMCs. Alternatively, the combination of FLLL32 and Herceptin promoted T helper-1 protective immune response. The combination of FLLL32 and Herceptin suppress the expression of immune checkpoints and provoke the T-helper1 immune response in lymphocytes. Our analysis indicates STAT3 as a promising target that improves Herceptin's role in breast cancer cell apoptosis.
期刊介绍:
This peer-reviewed international journal publishes original articles and reviews on all aspects of basic, translational and clinical immunology. The journal aims to provide high quality service to authors, and high quality articles for readers.
The journal accepts for publication material from investigators all over the world, which makes a significant contribution to basic, translational and clinical immunology.