Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity

Frontiers in Immunology

Immunology

Takao Iwawaki¹  María Rosa Bono²  Evelien Van De Velde³  Sofie Rennen³  Sophie Janssens³  Clint De Nolf⁴  Camila Fuentes⁵  Dominique Fernández⁶  Sandra Gaete González⁶  Fabiola Osorio⁶  Carolina Moreno⁶  Felipe Flores-Santibañez⁷  Diego Figueroa⁸  Álvaro Lladser⁹ 

[1] Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Kahoku, Japan;Immunology Laboratory, Biology Department, Faculty of Sciences, University of Chile, Santiago, Chile;Laboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, Belgium;Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium;Laboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, Belgium;Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium;Barriers in Inflammation, VIB Center for Inflammation Research, Ghent, Belgium;Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium;Laboratory of Cancer Immunoregulation, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile;Laboratory of Immunology and Cellular Stress, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile;Laboratory of Immunology and Cellular Stress, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile;Immunology Laboratory, Biology Department, Faculty of Sciences, University of Chile, Santiago, Chile;Laboratory of Immunoncology, Fundación Ciencia and Vida, Santiago, Chile;Laboratory of Immunoncology, Fundación Ciencia and Vida, Santiago, Chile;Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile;

关键词: dendritic cells;    immunity;    IRE1;    melanoma;    unfolded protein response;    XBP1;    cDC1;    antitumor immune response;   

DOI  :  10.3389/fimmu.2023.1209588

 received in 2023-04-20, accepted in 2023-05-23,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Flores-Santibañez, Rennen, Fernández, De Nolf, Van De Velde, Gaete González, Fuentes, Moreno, Figueroa, Lladser, Iwawaki, Bono, Janssens and Osorio