ArticleCell communication and signaling : CCS2026
Induction of caspase-mediated suppression of interferon signaling potentiates viral oncolysis of resistant tumor cells.
Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Cancer frenemy pathways: Inducing immunogenic cell death by exploiting apoptosis-interferon antagonism with oncolytic viruses.Molecular therapy. Oncology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
Tumors and cancer cell lines exhibit varying levels of activation in interferon (IFN) pathways and expression of IFN-stimulated genes (ISGs). This heterogeneity correlates with differential susceptibility to oncolytic viruses (OVs), which exploit impaired IFN responses to replicate in and kill malignant cells preferentially. A current challenge in oncolytic virotherapy (OVT) is to develop strategies that selectively inhibit IFN responses in malignant cells, thereby expanding the therapeutic range of OVs. This study proposes leveraging the vulnerability of tumor cells to BH3 mimetic compounds and caspase-mediated inhibition of IFN responses to enhance OVT in OV-resistant tumors. Analysis of the bladder cancer (BC) cohort from The Cancer Genome Atlas (TCGA) revealed a cluster of antiviral ISGs exhibiting positively correlated expression, and subpopulations of high- and low ISG expressors. A similar pattern was observed in the urinary tract cohort of the Cancer Cell Line Encyclopedia (CCLE), suggesting that this ISG expression profile is regulated in a cell-autonomous manner. We study two BC cell lines, T24 and UMUC3, differing in ISG expression, and SKMEL3 melanoma cells, a non-BC cell line with features similar to T24. T24 and SKMEL3 cells exhibited Janus kinase (JAK)-dependent resistance to the oncolytic orbivirus Epizootic Hemorrhagic Disease Virus Tel Aviv University (EHDV-TAU). Treatment with the BH3 mimetic Abt737 activated caspases, suppressed IFN-mediated antiviral responses, and enabled productive EHDV-TAU infection in tumor cells but not in normal fibroblasts. Mechanistically, Abt737 induced caspase-dependent cleavage of signal transduction Signal Transducer and Activator of Transcription 1 (STAT1) in both cell lines and interferon regulatory factor 3 (IRF3) in T24 cells, suggesting disruption of IFN/JAK/STAT signaling and IFN induction. In these cells, the EHDV-TAU + Abt737 combination increased the plasma membrane exposure of calreticulin and extracellular ATP, markers of immunogenic cell death. In contrast, combining Abt737 with a mutant vesicular stomatitis virus (VSVΔ51M) reduced viral titers, indicating virus-specific effects. This strategy appears optimal for OVs like EHDV-TAU, which thrive in apoptotic environments. Overall, this approach may broaden OVT’s therapeutic reach by leveraging apoptosis to overcome tumor antiviral resistance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.