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Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes...
The immunogenic effects of chemotherapy rely on effective activation of dendritic cells to present antigen to tumor-specific T cells. However, the signals that govern how dendritic cells seek out dying cancer cells to initiate this process are poorly understood. A recent study by Vacchelli et al. provides important insight.
MCL1, which encodes the antiapoptotic protein MCL1, is among the most frequently amplified genes in human cancer. A chemical genomic screen identified compounds, including anthracyclines, that decreased MCL1 expression. Genomic profiling indicated that these compounds were global transcriptional repressors that preferentially affect MCL1 due to its short mRNA half-life. Transcriptional repressors...
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