Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity
In cancer, activation of the IRE1/XBP1s axis of the unfolded protein response (UPR) promotes immunosuppression and tumor growth, by acting in cancer cells and tumor infiltrating immune cells. However, the role of IRE1/XBP1s in dendritic cells (DCs) in tumors, particularly in conventional type 1 DCs...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1209588/full |
| _version_ | 1797810582121873408 |
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| author | Felipe Flores-Santibañez Felipe Flores-Santibañez Sofie Rennen Sofie Rennen Dominique Fernández Clint De Nolf Clint De Nolf Clint De Nolf Clint De Nolf Evelien Van De Velde Evelien Van De Velde Sandra Gaete González Camila Fuentes Carolina Moreno Diego Figueroa Álvaro Lladser Álvaro Lladser Takao Iwawaki María Rosa Bono Sophie Janssens Sophie Janssens Fabiola Osorio |
| author_facet | Felipe Flores-Santibañez Felipe Flores-Santibañez Sofie Rennen Sofie Rennen Dominique Fernández Clint De Nolf Clint De Nolf Clint De Nolf Clint De Nolf Evelien Van De Velde Evelien Van De Velde Sandra Gaete González Camila Fuentes Carolina Moreno Diego Figueroa Álvaro Lladser Álvaro Lladser Takao Iwawaki María Rosa Bono Sophie Janssens Sophie Janssens Fabiola Osorio |
| author_sort | Felipe Flores-Santibañez |
| collection | DOAJ |
| description | In cancer, activation of the IRE1/XBP1s axis of the unfolded protein response (UPR) promotes immunosuppression and tumor growth, by acting in cancer cells and tumor infiltrating immune cells. However, the role of IRE1/XBP1s in dendritic cells (DCs) in tumors, particularly in conventional type 1 DCs (cDC1s) which are cellular targets in immunotherapy, has not been fully elucidated. Here, we studied the role of IRE1/XBP1s in subcutaneous B16/B78 melanoma and MC38 tumors by generating loss-of-function models of IRE1 and/or XBP1s in DCs or in cDC1s. Data show that concomitant deletion of the RNase domain of IRE1 and XBP1s in DCs and cDC1s does not influence the kinetics of B16/B78 and MC38 tumor growth or the effector profile of tumor infiltrating T cells. A modest effect is observed in mice bearing single deletion of XBP1s in DCs, which showed slight acceleration of melanoma tumor growth and dysfunctional T cell responses, however, this effect was not recapitulated in animals lacking XBP1 only in cDC1s. Thus, evidence presented here argues against a general pro-tumorigenic role of the IRE1/XBP1s pathway in tumor associated DC subsets. |
| first_indexed | 2024-03-13T07:09:56Z |
| format | Article |
| id | doaj.art-989ab48b82084085b311233598ad7ae2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T07:09:56Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-989ab48b82084085b311233598ad7ae22023-06-06T04:33:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.12095881209588Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunityFelipe Flores-Santibañez0Felipe Flores-Santibañez1Sofie Rennen2Sofie Rennen3Dominique Fernández4Clint De Nolf5Clint De Nolf6Clint De Nolf7Clint De Nolf8Evelien Van De Velde9Evelien Van De Velde10Sandra Gaete González11Camila Fuentes12Carolina Moreno13Diego Figueroa14Álvaro Lladser15Álvaro Lladser16Takao Iwawaki17María Rosa Bono18Sophie Janssens19Sophie Janssens20Fabiola Osorio21Laboratory of Immunology and Cellular Stress, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, ChileImmunology Laboratory, Biology Department, Faculty of Sciences, University of Chile, Santiago, ChileLaboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, BelgiumDepartment of Internal Medicine and Pediatrics, Ghent University, Ghent, BelgiumLaboratory of Immunology and Cellular Stress, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, ChileLaboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, BelgiumDepartment of Internal Medicine and Pediatrics, Ghent University, Ghent, BelgiumBarriers in Inflammation, VIB Center for Inflammation Research, Ghent, BelgiumDepartment of Biomedical Molecular Biology, Ghent University, Ghent, BelgiumLaboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, BelgiumDepartment of Internal Medicine and Pediatrics, Ghent University, Ghent, BelgiumLaboratory of Immunology and Cellular Stress, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, ChileLaboratory of Cancer Immunoregulation, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, ChileLaboratory of Immunology and Cellular Stress, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, ChileLaboratory of Immunoncology, Fundación Ciencia and Vida, Santiago, ChileLaboratory of Immunoncology, Fundación Ciencia and Vida, Santiago, ChileFacultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile0Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Kahoku, JapanImmunology Laboratory, Biology Department, Faculty of Sciences, University of Chile, Santiago, ChileLaboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, BelgiumDepartment of Internal Medicine and Pediatrics, Ghent University, Ghent, BelgiumLaboratory of Immunology and Cellular Stress, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, ChileIn cancer, activation of the IRE1/XBP1s axis of the unfolded protein response (UPR) promotes immunosuppression and tumor growth, by acting in cancer cells and tumor infiltrating immune cells. However, the role of IRE1/XBP1s in dendritic cells (DCs) in tumors, particularly in conventional type 1 DCs (cDC1s) which are cellular targets in immunotherapy, has not been fully elucidated. Here, we studied the role of IRE1/XBP1s in subcutaneous B16/B78 melanoma and MC38 tumors by generating loss-of-function models of IRE1 and/or XBP1s in DCs or in cDC1s. Data show that concomitant deletion of the RNase domain of IRE1 and XBP1s in DCs and cDC1s does not influence the kinetics of B16/B78 and MC38 tumor growth or the effector profile of tumor infiltrating T cells. A modest effect is observed in mice bearing single deletion of XBP1s in DCs, which showed slight acceleration of melanoma tumor growth and dysfunctional T cell responses, however, this effect was not recapitulated in animals lacking XBP1 only in cDC1s. Thus, evidence presented here argues against a general pro-tumorigenic role of the IRE1/XBP1s pathway in tumor associated DC subsets.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1209588/fulldendritic cellsimmunityIRE1melanomaunfolded protein responseXBP1 |
| spellingShingle | Felipe Flores-Santibañez Felipe Flores-Santibañez Sofie Rennen Sofie Rennen Dominique Fernández Clint De Nolf Clint De Nolf Clint De Nolf Clint De Nolf Evelien Van De Velde Evelien Van De Velde Sandra Gaete González Camila Fuentes Carolina Moreno Diego Figueroa Álvaro Lladser Álvaro Lladser Takao Iwawaki María Rosa Bono Sophie Janssens Sophie Janssens Fabiola Osorio Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity Frontiers in Immunology dendritic cells immunity IRE1 melanoma unfolded protein response XBP1 |
| title | Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity |
| title_full | Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity |
| title_fullStr | Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity |
| title_full_unstemmed | Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity |
| title_short | Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity |
| title_sort | nuanced role for dendritic cell intrinsic ire1 rnase in the regulation of antitumor adaptive immunity |
| topic | dendritic cells immunity IRE1 melanoma unfolded protein response XBP1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1209588/full |
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