IRF8-mutant B cell lymphoma evades immunity through a CD74-dependent deregulation of antigen processing and presentation in MHCII complexes.

Autor: Qiu Z; Division of Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Khalife J; Division of Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Ethiraj P; Division of Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Jaafar C; Division of Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Lin AP; Division of Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Holder KN; Department of Pathology, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Ritter JP; Department of Pathology, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Chiou L; Division of Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Huelgas-Morales G; Division of Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Aslam S; Division of Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Zhang Z; Department of Molecular Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Liu Z; Department of Molecular Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Arya S; Department of Biochemistry and Structural Biology, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Gupta YK; Department of Biochemistry and Structural Biology, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Dahia PLM; Division of Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA., Aguiar RCT; Division of Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA.; South Texas Veterans Health Care System, Audie Murphy VA Hospital, San Antonio, TX 78229, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Jul 12; Vol. 10 (28), pp. eadk2091. Date of Electronic Publication: 2024 Jul 12.
DOI: 10.1126/sciadv.adk2091
Abstrakt: The mechanism by which interferon regulatory factor 8 (IRF8) mutation contributes to lymphomagenesis is unknown. We modeled IRF8 variants in B cell lymphomas and found that they affected the expression of regulators of antigen presentation. Expression of IRF8 mutants in murine B cell lymphomas suppressed CD4, but not CD8, activation elicited by antigen presentation and downmodulated CD74 and human leukocyte antigen (HLA) DM, intracellular regulators of antigen peptide processing/loading in the major histocompatibility complex (MHC) II. Concordantly, mutant IRF8 bound less efficiently to the promoters of these genes. Mice harboring IRF8 mutant lymphomas displayed higher tumor burden and remodeling of the tumor microenvironment, typified by depletion of CD4, CD8, and natural killer cells, increase in regulatory T cells and T follicular helper cells. Deconvolution of bulk RNA sequencing data from IRF8-mutant human diffuse large B cell lymphoma (DLBCL) recapitulated part of the immune remodeling detected in mice. We concluded that IRF8 mutations contribute to DLBCL biology by facilitating immune escape.
Databáze: MEDLINE