صورة
Image_4_The β-carboline Harmine improves the therapeutic benefit of anti-PD1 in melanoma by increasing the MHC-I-dependent antigen presentation.jpeg
| العنوان: | Image_4_The β-carboline Harmine improves the therapeutic benefit of anti-PD1 in melanoma by increasing the MHC-I-dependent antigen presentation.jpeg |
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| المؤلفون: | Muhammad Zaeem Noman, Irene Adelaide Bocci, Manale Karam, Kris Van Moer, Manon Bosseler, Akinchan Kumar, Guy Berchem, Christian Auclair, Bassam Janji |
| سنة النشر: | 2022 |
| المجموعة: | Frontiers: Figshare |
| مصطلحات موضوعية: | Immunology, Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies), Autoimmunity, Cellular Immunology, Humoural Immunology and Immunochemistry, Immunogenetics (incl. Genetic Immunology), Innate Immunity, Transplantation Immunology, Tumour Immunology, Immunology not elsewhere classified, Genetic Immunology, Animal Immunology, Veterinary Immunology, MHC-I antigen presentation, harmine, DYRK1A, anti-PD1 Immunotherapy, T lymphocyte and NK cells infiltration, melanoma, inflammatory chemokines |
| الوصف: | Harmine is a dual-specificity tyrosine-regulated kinase 1A (DYRK1A) inhibitor that displays a number of biological and pharmacological properties. Also referred to as ACB1801 molecule, we have previously reported that harmine increases the presentation of major histocompatibility complex (MHC)-I-dependent antigen on melanoma cells. Here, we show that ACB1801 upregulates the mRNA expression of several proteins of the MHC-I such as Transporter Associated with antigen Processing TAP1 and 2, Tapasin and Lmp2 (hereafter referred to as MHC-I signature) in melanoma cells. Treatment of mice bearing melanoma B16-F10 with ACB1801 inhibits the growth and weight of tumors and induces a profound modification of the tumor immune landscape. Strikingly, combining ACB1801 with anti-PD1 significantly improves its therapeutic benefit in B16-F10 melanoma-bearing mice. These results suggest that, by increasing the MHC-I, ACB1801 can be combined with anti-PD1/PD-L1 therapy to improve the survival benefit in cancer patients displaying a defect in MHC-I expression. This is further supported by data showing that i) high expression levels of TAP1, Tapasin and Lmp2 was observed in melanoma patients that respond to anti-PD1; ii) the survival is significantly improved in melanoma patients who express high MHC-I signature relative to those expressing low MHC-I signature; and iii) high expression of MHC-I signature in melanoma patients was correlated with increased expression of CD8 and NK cell markers and overexpression of proinflammatory chemokines involved in the recruitment of CD8+ T cells. |
| نوع الوثيقة: | still image |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/figure/Image_4_The_-carboline_Harmine_improves_the_therapeutic_benefit_of_anti-PD1_in_melanoma_by_increasing_the_MHC-I-dependent_antigen_presentation_jpeg/21556164Test |
| DOI: | 10.3389/fimmu.2022.980704.s005 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2022.980704.s005Test https://figshare.com/articles/figure/Image_4_The_-carboline_Harmine_improves_the_therapeutic_benefit_of_anti-PD1_in_melanoma_by_increasing_the_MHC-I-dependent_antigen_presentation_jpeg/21556164Test |
| حقوق: | CC BY 4.0 |
| رقم الانضمام: | edsbas.33F15974 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2022.980704.s005 |
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