E-MTAB-5028 - Analysis of mouse T cell transcription profile after co-culture with BaF3 cells with or without the oncogenic point mutation JAK2 V617F

Status
Submitted on 14 June 2016, last updated on 30 November 2018, released on 1 December 2018
Organism
Mus musculus
Samples (7)
Array (1)
Protocols (7)
Description
The activation of PD-1 (Programmed Death receptor-1) on T cells can cause T cell exhaustion and immune tolerance. Some tumors up-regulate the expression of the ligand of PD-1, namely PD-L1 (Programmed Death Receptor-Ligand 1), thus preventing anti-tumor immune response and promoting immune-escape. Previous studies have shown that JAK2 (Janus Kinase 2) signaling can promote PD-L1 expression in Hodgkin Lymphoma. In Myeloproliferative Neoplasms (MPN), JAK2 is frequently characterized by the the presence of the point-mutation V617F, which leads to its constitutive activation and to uncontrolled cell proliferation and survival. Accordingly, tumor cell lines expressing JAK2 V617F express higher levels of PD-L1 as compared to tumor cell lines negative for such mutations. In this experiment, we transfected BaF3 cells with a vector (plasmid for Murine Stem Cell Virus) containing the gene for JAK2 with the point-mutation V617F. As control, we used BaF3 cells transfected with the same vector, but without the gene for JAK2 V617F (empty vector). Both the cell lines (with/without JAK2 V617F) were co-cultured with primary murine T cells. When co-cultured with BaF3 cells expressing JAK2 V617F, T cells upregulated genes connected to senescence pathways, showed increased apoptosis, less cytokine production, and displayed other forms of dysfunction which can be associated with the activation of PD-1.
Experiment types
transcription profiling by array, stimulus or stress design
Contacts
Citation
Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. Prestipino A, Emhardt AJ, Aumann K, O'Sullivan D, Gorantla SP, Duquesne S, Melchinger W, Braun L, Vuckovic S, Boerries M, Busch H, Halbach S, Pennisi S, Poggio T, Apostolova P, Veratti P, Hettich M, Niedermann G, Bartholomä M, Shoumariyeh K, Jutzi JS, Wehrle J, Dierks C, Becker H, Schmitt-Graeff A, Follo M, Pfeifer D, Rohr J, Fuchs S, Ehl S, Hartl FA, Minguet S, Miething C, Heidel FH, Kröger N, Triviai I, Brummer T, Finke J, Illert AL, Ruggiero E, Bonini C, Duyster J, Pahl HL, Lane SW, Hill GR, Blazar BR, von Bubnoff N, Pearce EL, Zeiser R. 10(429) (2018), PMID:29467301
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-MTAB-5028.idf.txt
Sample and data relationshipE-MTAB-5028.sdrf.txt
Raw data (1)E-MTAB-5028.raw.1.zip
Array designA-GEOD-17408.adf.txt
Links