Jörg Hänze, Johannes Schulte-Herbrüggen, Rainer Hofmann, Axel Hegele
{"title":"细胞抑制剂对干扰素 γ 诱导的尿路癌和活化 T 淋巴细胞中免疫检查点调节因子的调节","authors":"Jörg Hänze, Johannes Schulte-Herbrüggen, Rainer Hofmann, Axel Hegele","doi":"10.1038/s41435-023-00203-0","DOIUrl":null,"url":null,"abstract":"Exploring the regulation of co-inhibitory (PD-1, PD-L1, CTLA-4) and co-stimulatory (CD28) genes by chemotherapeutic drugs is important for combined immune checkpoint blockade (ICB) therapy. ICB interferes with T-cell receptor and major histocompatibility complex (MHC) signaling by antibody drugs directed against the co-inhibitors. Here, we analyzed urothelial (T24) cell line with respect to cytokine signaling by interferon γ (IFNG) and the leukemia lymphocyte (Jurkat) cell line with respect to T-cell activation as mimicked by phorbolester and calcium ionophore (pma/iono). Alongside, we considered possible intervention with the chemotherapeutics gemcitabine, cisplatin and vinflunine. Noteworthy, cisplatin significantly induced PD-L1-mRNA in naïve and IFNG treated cells whereas gemcitabine and vinflunine had no effect on PD-L1-mRNA. At the protein level, PD-L1 showed typical induction in IFNG treated cells. In Jurkat cells, cisplatin significantly induced PD-1-mRNA and PD-L1-mRNA. Pma/iono administration did not alter PD-1-mRNA and PD-L1-mRNA but significantly increased CTLA-4-mRNA and CD28-mRNA levels where vinflunine suppressed the CD28-mRNA induction. In sum, we demonstrated that certain cytostatic drugs being relevant for the therapy of urothelial cancer, affect co-inhibitory and co-stimulatory modulators of immune signaling with potential impact for perspective combined ICB therapy of patients.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2023-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266969/pdf/","citationCount":"0","resultStr":"{\"title\":\"Modulation of immune checkpoint regulators in interferon γ induced urothelial carcinoma and activated T-lymphocyte cells by cytostatics\",\"authors\":\"Jörg Hänze, Johannes Schulte-Herbrüggen, Rainer Hofmann, Axel Hegele\",\"doi\":\"10.1038/s41435-023-00203-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Exploring the regulation of co-inhibitory (PD-1, PD-L1, CTLA-4) and co-stimulatory (CD28) genes by chemotherapeutic drugs is important for combined immune checkpoint blockade (ICB) therapy. ICB interferes with T-cell receptor and major histocompatibility complex (MHC) signaling by antibody drugs directed against the co-inhibitors. Here, we analyzed urothelial (T24) cell line with respect to cytokine signaling by interferon γ (IFNG) and the leukemia lymphocyte (Jurkat) cell line with respect to T-cell activation as mimicked by phorbolester and calcium ionophore (pma/iono). Alongside, we considered possible intervention with the chemotherapeutics gemcitabine, cisplatin and vinflunine. Noteworthy, cisplatin significantly induced PD-L1-mRNA in naïve and IFNG treated cells whereas gemcitabine and vinflunine had no effect on PD-L1-mRNA. At the protein level, PD-L1 showed typical induction in IFNG treated cells. In Jurkat cells, cisplatin significantly induced PD-1-mRNA and PD-L1-mRNA. Pma/iono administration did not alter PD-1-mRNA and PD-L1-mRNA but significantly increased CTLA-4-mRNA and CD28-mRNA levels where vinflunine suppressed the CD28-mRNA induction. In sum, we demonstrated that certain cytostatic drugs being relevant for the therapy of urothelial cancer, affect co-inhibitory and co-stimulatory modulators of immune signaling with potential impact for perspective combined ICB therapy of patients.\",\"PeriodicalId\":12691,\"journal\":{\"name\":\"Genes and immunity\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2023-05-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266969/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genes and immunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41435-023-00203-0\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes and immunity","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41435-023-00203-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Modulation of immune checkpoint regulators in interferon γ induced urothelial carcinoma and activated T-lymphocyte cells by cytostatics
Exploring the regulation of co-inhibitory (PD-1, PD-L1, CTLA-4) and co-stimulatory (CD28) genes by chemotherapeutic drugs is important for combined immune checkpoint blockade (ICB) therapy. ICB interferes with T-cell receptor and major histocompatibility complex (MHC) signaling by antibody drugs directed against the co-inhibitors. Here, we analyzed urothelial (T24) cell line with respect to cytokine signaling by interferon γ (IFNG) and the leukemia lymphocyte (Jurkat) cell line with respect to T-cell activation as mimicked by phorbolester and calcium ionophore (pma/iono). Alongside, we considered possible intervention with the chemotherapeutics gemcitabine, cisplatin and vinflunine. Noteworthy, cisplatin significantly induced PD-L1-mRNA in naïve and IFNG treated cells whereas gemcitabine and vinflunine had no effect on PD-L1-mRNA. At the protein level, PD-L1 showed typical induction in IFNG treated cells. In Jurkat cells, cisplatin significantly induced PD-1-mRNA and PD-L1-mRNA. Pma/iono administration did not alter PD-1-mRNA and PD-L1-mRNA but significantly increased CTLA-4-mRNA and CD28-mRNA levels where vinflunine suppressed the CD28-mRNA induction. In sum, we demonstrated that certain cytostatic drugs being relevant for the therapy of urothelial cancer, affect co-inhibitory and co-stimulatory modulators of immune signaling with potential impact for perspective combined ICB therapy of patients.
期刊介绍:
Genes & Immunity emphasizes studies investigating how genetic, genomic and functional variations affect immune cells and the immune system, and associated processes in the regulation of health and disease. It further highlights articles on the transcriptional and posttranslational control of gene products involved in signaling pathways regulating immune cells, and protective and destructive immune responses.