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1
المؤلفون: Meriem Hasmim, Malina Xiao, Kris Van Moer, Akinchan Kumar, Alexandra Oniga, Michel Mittelbronn, Caroline Duhem, Anwar Chammout, Guy Berchem, Jean Paul Thiery, Marianna Volpert, Brett Hollier, Muhammad Zaeem Noman, Bassam Janji
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, CD73, SNAI1, epithelial-to-mesenchymal transition, adenosine, anti-tumor immune response, immunotherapy, breast cancer, immune checkpoints
الوصف: Triple-negative subtype of breast cancer (TNBC) is hallmarked by frequent disease relapse and shows highest mortality rate. Although PD-1/PD-L1 immune checkpoint blockades have recently shown promising clinical benefits, the overall response rate remains largely insufficient. Hence, alternative therapeutic approaches are warranted. Given the immunosuppressive properties of CD73-mediated adenosine release, CD73 blocking approaches are emerging as attractive strategies in cancer immunotherapy. Understanding the precise mechanism regulating the expression of CD73 is required to develop effective anti-CD73-based therapy. Our previous observations demonstrate that the transcription factors driving epithelial-to-mesenchymal transition (EMT-TF) can regulate the expression of several inhibitory immune checkpoints. Here we analyzed the role of the EMT-TF SNAI1 in the regulation of CD73 in TNBC cells. We found that doxycycline-driven SNAI1 expression in the epithelial -like TNBC cell line MDA-MB-468 results in CD73 upregulation by direct binding to the CD73 proximal promoter. SNAI1-dependent upregulation of CD73 leads to increased production and release of extracellular adenosine by TNBC cells and contributes to the enhancement of TNBC immunosuppressive properties. Our data are validated in TNBC samples by showing a positive correlation between the mRNA expression of CD73 and SNAI1. Overall, our results reveal a new CD73 regulation mechanism in TNBC that participates in TNBC-mediated immunosuppression and paves the way for developing new treatment opportunities for CD73-positive TNBC.
الإتاحة: https://doi.org/10.3389/fimmu.2022.982821.s004Test
https://figshare.com/articles/dataset/Table_1_SNAI1-dependent_upregulation_of_CD73_increases_extracellular_adenosine_release_to_mediate_immune_suppression_in_TNBC_xlsx/21069094Test -
2صورة
المؤلفون: Meriem Hasmim, Malina Xiao, Kris Van Moer, Akinchan Kumar, Alexandra Oniga, Michel Mittelbronn, Caroline Duhem, Anwar Chammout, Guy Berchem, Jean Paul Thiery, Marianna Volpert, Brett Hollier, Muhammad Zaeem Noman, Bassam Janji
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, CD73, SNAI1, epithelial-to-mesenchymal transition, adenosine, anti-tumor immune response, immunotherapy, breast cancer, immune checkpoints
الوصف: Triple-negative subtype of breast cancer (TNBC) is hallmarked by frequent disease relapse and shows highest mortality rate. Although PD-1/PD-L1 immune checkpoint blockades have recently shown promising clinical benefits, the overall response rate remains largely insufficient. Hence, alternative therapeutic approaches are warranted. Given the immunosuppressive properties of CD73-mediated adenosine release, CD73 blocking approaches are emerging as attractive strategies in cancer immunotherapy. Understanding the precise mechanism regulating the expression of CD73 is required to develop effective anti-CD73-based therapy. Our previous observations demonstrate that the transcription factors driving epithelial-to-mesenchymal transition (EMT-TF) can regulate the expression of several inhibitory immune checkpoints. Here we analyzed the role of the EMT-TF SNAI1 in the regulation of CD73 in TNBC cells. We found that doxycycline-driven SNAI1 expression in the epithelial -like TNBC cell line MDA-MB-468 results in CD73 upregulation by direct binding to the CD73 proximal promoter. SNAI1-dependent upregulation of CD73 leads to increased production and release of extracellular adenosine by TNBC cells and contributes to the enhancement of TNBC immunosuppressive properties. Our data are validated in TNBC samples by showing a positive correlation between the mRNA expression of CD73 and SNAI1. Overall, our results reveal a new CD73 regulation mechanism in TNBC that participates in TNBC-mediated immunosuppression and paves the way for developing new treatment opportunities for CD73-positive TNBC.
الإتاحة: https://doi.org/10.3389/fimmu.2022.982821.s002Test
https://figshare.com/articles/figure/Image_2_SNAI1-dependent_upregulation_of_CD73_increases_extracellular_adenosine_release_to_mediate_immune_suppression_in_TNBC_jpg/21069088Test -
3صورة
المؤلفون: Meriem Hasmim, Malina Xiao, Kris Van Moer, Akinchan Kumar, Alexandra Oniga, Michel Mittelbronn, Caroline Duhem, Anwar Chammout, Guy Berchem, Jean Paul Thiery, Marianna Volpert, Brett Hollier, Muhammad Zaeem Noman, Bassam Janji
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, CD73, SNAI1, epithelial-to-mesenchymal transition, adenosine, anti-tumor immune response, immunotherapy, breast cancer, immune checkpoints
الوصف: Triple-negative subtype of breast cancer (TNBC) is hallmarked by frequent disease relapse and shows highest mortality rate. Although PD-1/PD-L1 immune checkpoint blockades have recently shown promising clinical benefits, the overall response rate remains largely insufficient. Hence, alternative therapeutic approaches are warranted. Given the immunosuppressive properties of CD73-mediated adenosine release, CD73 blocking approaches are emerging as attractive strategies in cancer immunotherapy. Understanding the precise mechanism regulating the expression of CD73 is required to develop effective anti-CD73-based therapy. Our previous observations demonstrate that the transcription factors driving epithelial-to-mesenchymal transition (EMT-TF) can regulate the expression of several inhibitory immune checkpoints. Here we analyzed the role of the EMT-TF SNAI1 in the regulation of CD73 in TNBC cells. We found that doxycycline-driven SNAI1 expression in the epithelial -like TNBC cell line MDA-MB-468 results in CD73 upregulation by direct binding to the CD73 proximal promoter. SNAI1-dependent upregulation of CD73 leads to increased production and release of extracellular adenosine by TNBC cells and contributes to the enhancement of TNBC immunosuppressive properties. Our data are validated in TNBC samples by showing a positive correlation between the mRNA expression of CD73 and SNAI1. Overall, our results reveal a new CD73 regulation mechanism in TNBC that participates in TNBC-mediated immunosuppression and paves the way for developing new treatment opportunities for CD73-positive TNBC.
الإتاحة: https://doi.org/10.3389/fimmu.2022.982821.s001Test
https://figshare.com/articles/figure/Image_1_SNAI1-dependent_upregulation_of_CD73_increases_extracellular_adenosine_release_to_mediate_immune_suppression_in_TNBC_jpeg/21069085Test -
4صورة
المؤلفون: Meriem Hasmim, Malina Xiao, Kris Van Moer, Akinchan Kumar, Alexandra Oniga, Michel Mittelbronn, Caroline Duhem, Anwar Chammout, Guy Berchem, Jean Paul Thiery, Marianna Volpert, Brett Hollier, Muhammad Zaeem Noman, Bassam Janji
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, CD73, SNAI1, epithelial-to-mesenchymal transition, adenosine, anti-tumor immune response, immunotherapy, breast cancer, immune checkpoints
الوصف: Triple-negative subtype of breast cancer (TNBC) is hallmarked by frequent disease relapse and shows highest mortality rate. Although PD-1/PD-L1 immune checkpoint blockades have recently shown promising clinical benefits, the overall response rate remains largely insufficient. Hence, alternative therapeutic approaches are warranted. Given the immunosuppressive properties of CD73-mediated adenosine release, CD73 blocking approaches are emerging as attractive strategies in cancer immunotherapy. Understanding the precise mechanism regulating the expression of CD73 is required to develop effective anti-CD73-based therapy. Our previous observations demonstrate that the transcription factors driving epithelial-to-mesenchymal transition (EMT-TF) can regulate the expression of several inhibitory immune checkpoints. Here we analyzed the role of the EMT-TF SNAI1 in the regulation of CD73 in TNBC cells. We found that doxycycline-driven SNAI1 expression in the epithelial -like TNBC cell line MDA-MB-468 results in CD73 upregulation by direct binding to the CD73 proximal promoter. SNAI1-dependent upregulation of CD73 leads to increased production and release of extracellular adenosine by TNBC cells and contributes to the enhancement of TNBC immunosuppressive properties. Our data are validated in TNBC samples by showing a positive correlation between the mRNA expression of CD73 and SNAI1. Overall, our results reveal a new CD73 regulation mechanism in TNBC that participates in TNBC-mediated immunosuppression and paves the way for developing new treatment opportunities for CD73-positive TNBC.
الإتاحة: https://doi.org/10.3389/fimmu.2022.982821.s003Test
https://figshare.com/articles/figure/Image_3_SNAI1-dependent_upregulation_of_CD73_increases_extracellular_adenosine_release_to_mediate_immune_suppression_in_TNBC_jpeg/21069091Test -
5
المؤلفون: Muhammad Zaeem Noman, Irene Adelaide Bocci, Manale Karam, Kris Van Moer, Manon Bosseler, Akinchan Kumar, Guy Berchem, Christian Auclair, Bassam Janji
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.
الإتاحة: https://doi.org/10.3389/fimmu.2022.980704.s007Test
https://figshare.com/articles/dataset/Table_2_The_-carboline_Harmine_improves_the_therapeutic_benefit_of_anti-PD1_in_melanoma_by_increasing_the_MHC-I-dependent_antigen_presentation_xlsx/21556170Test -
6صورة
المؤلفون: Muhammad Zaeem Noman, Irene Adelaide Bocci, Manale Karam, Kris Van Moer, Manon Bosseler, Akinchan Kumar, Guy Berchem, Christian Auclair, Bassam Janji
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.
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 -
7صورة
المؤلفون: Muhammad Zaeem Noman, Irene Adelaide Bocci, Manale Karam, Kris Van Moer, Manon Bosseler, Akinchan Kumar, Guy Berchem, Christian Auclair, Bassam Janji
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.
الإتاحة: https://doi.org/10.3389/fimmu.2022.980704.s003Test
https://figshare.com/articles/figure/Image_2_The_-carboline_Harmine_improves_the_therapeutic_benefit_of_anti-PD1_in_melanoma_by_increasing_the_MHC-I-dependent_antigen_presentation_jpeg/21556158Test -
8صورة
المؤلفون: Muhammad Zaeem Noman, Irene Adelaide Bocci, Manale Karam, Kris Van Moer, Manon Bosseler, Akinchan Kumar, Guy Berchem, Christian Auclair, Bassam Janji
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.
الإتاحة: https://doi.org/10.3389/fimmu.2022.980704.s004Test
https://figshare.com/articles/figure/Image_3_The_-carboline_Harmine_improves_the_therapeutic_benefit_of_anti-PD1_in_melanoma_by_increasing_the_MHC-I-dependent_antigen_presentation_jpeg/21556161Test -
9
المؤلفون: Muhammad Zaeem Noman, Irene Adelaide Bocci, Manale Karam, Kris Van Moer, Manon Bosseler, Akinchan Kumar, Guy Berchem, Christian Auclair, Bassam Janji
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.
الإتاحة: https://doi.org/10.3389/fimmu.2022.980704.s001Test
https://figshare.com/articles/dataset/DataSheet_1_The_-carboline_Harmine_improves_the_therapeutic_benefit_of_anti-PD1_in_melanoma_by_increasing_the_MHC-I-dependent_antigen_presentation_docx/21556152Test -
10
المؤلفون: Muhammad Zaeem Noman, Irene Adelaide Bocci, Manale Karam, Kris Van Moer, Manon Bosseler, Akinchan Kumar, Guy Berchem, Christian Auclair, Bassam Janji
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.
الإتاحة: https://doi.org/10.3389/fimmu.2022.980704.s006Test
https://figshare.com/articles/dataset/Table_1_The_-carboline_Harmine_improves_the_therapeutic_benefit_of_anti-PD1_in_melanoma_by_increasing_the_MHC-I-dependent_antigen_presentation_xlsx/21556167Test
