An oncogenic axis of STAT-mediated BATF3 upregulation causing MYC activity in classical Hodgkin and anaplastic large cell lymphoma.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE93862 | GEO | 2018/01/08
SECONDARY ACCESSION(S): PRJNA362616
REPOSITORIES: GEO
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Project description:The transcription factor network in Hodgkin lymphoma (HL) represents a unique composition of proteins found in no other hematopoietic cell. An aberrant downregulation of the B cell transcription factor EBF1 is observed in the B cell-derived Hodgkin and Reed/Sternberg (HRS) tumor cells. Herein, we elucidated the consequences of the down regulation of this factor in HL. To obtain a more comprehensive overview of EBF1 regulated genes in cHL cell lines, we performed a gene chip analysis comparing gene expression in tGFP-EBF1-transduced L-1236 and L-428 cells compared to samples transduced with vectors encoding only tGFP. 12 total samples were analyzed. Three independent samples were analyzed per condition and cell line.We generated the following pairwise comparisons using Bioconductor: tGFP-EBF1 L-428 < tGFP L-428; tGFP-EBF1 L-1236 < tGFP L-1236. Genes with an FDR≤ 5 % and a fold-change ≥ 2.0 and ≤ -2.0 were selected.
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Project description:Anti-viral CD8 T cell responses are characterized by an initial activation/priming of T lymphocytes followed by a massive proliferation, subset differentiation, population contraction and the development of a stable memory pool. The transcription factor BATF3 has been shown to play a central role in the development of conventional dendritic cells (cDC1), which in turn are critical for the optimal priming of CD8 T cells. Here we show that BATF3 is expressed within the first days after priming but has long-lasting T cell intrinsic effects. We found that T cells that lack Batf3 show a normal expansion and differentiation, yet succumbed to an aggravated contraction and had a diminished memory response. Vice versa BATF3-overexpression in CD8 T cells promoted their survival and transition to memory. Mechanistically, BATF3 regulates T cell apoptosis and longevity via the proapoptotic factor BIM. By programing CD8 T cell survival and memory, BATF3 is a promising molecule to optimize adoptive T cell therapy in patients.
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