IRF2BP2-mediated MHC-I expression controls cytotoxic T cell responses in acute myeloid leukemia [RNA-Seq]

Immunotherapy, including immune checkpoint blockade (ICB), has become an effective option for treating patients with cancer, especially those with solid tumors. Recently, T cell-based cellular therapies have extended the scope of immunotherapy to B-cell malignancies. Immunotherapy options for patients with acute myeloid leukemia (AML), however, are limited. To identify new immunotherapy approaches for AML, we performed CRISPR/Cas9 AML T cell co-culture screens. We determined that depletion of the transcription factor IRF2BP2 leads to enhanced T cell killing both in vitro and in vivo. Gene expression profiling and flow cytometry studies confirmed enhanced MHC-I expression upon IRF2BP2 loss. Chromatin binding analysis further revealed a regulatory axis whereby MHC-I expression is repressed by IRF2BP2 through its repression of the interferon alpha pathway. Our studies have identified the inhibition of IRF2BP2 as a potential strategy for enhancing T-cell-based therapies in patients with AML Overall design: To investigate the transcriptional regulation function of IRF2BP2 in acute myeloid leukemia, we established THP-1 and MOLM-13 human AML cell lines with control and IRF2BP2 knockout using sgRNAs. We then acquired gene expression profiles of these cell lines by performing RNA-seq.