106 Multiplex epitranscriptomic profiling reveals RNA modification signatures of immune activation and therapeutic response in cancer immunology
Year: 2026
Type: conference-abstract
Abstract: Background RNA modifications regulate innate and adaptive immunity by controlling RNA stability, translation, and antiviral signaling pathways. Multiple RNA-modifying enzymes, including ADAR1 and METTL3, have emerged as promising immuno-oncology drug targets, and inhibition of ADAR1 has been shown to enhance responses to the immune checkpoint blockade. However, technologies capable of measuring multiple RNA modifications simultaneously to characterize immune states remain limited. We developed EpiPlex, a sequencing-based platform that quantitatively profiles N6-methyladenosine (m6A), inosine and pseudouridine in a single assay to interrogate immune regulation and therapeutic responses.Methods EpiPlex was applied to immune cell populations and cancer cell models to characterize epitranscriptomic differences associated with immune cell identity, T-cell activation, and pharmacologic inhibition of METTL3-mediated pathways. RNA modification profiles were analyzed alongside transcriptional changes to identify biologically relevant immune signatures.Results We identified distinct, cell type-specific epitranscriptomic landscapes across immune populations, demonstrating that RNA modification patterns reflect immune cell identity. T-cell activation induced reproducible changes in m6A signatures, consistent with dynamic epitranscriptomic remodeling during adaptive immune responses. In ovarian tumor cell models, pharmacologic inhibition of METTL3 resulted in activation of innate immune signaling, including induction of the RIG-I pathway, accompanied by characteristic changes of m6A and inosine profiles. These findings demonstrate that EpiPlex captures both adaptive and innate immune responses and provides direct molecular readouts of perturbations in RNA modification pathways targeted by emerging immunotherapies.Conclusions The epitranscriptome constitutes an additional layer of immune regulation that complements the genome and transcriptome. Characterizing RNA modification dynamics may improve our understanding of anti-tumor immunityss, facilitate biomarker discovery, and accelerate development of immunotherapies targeting RNA-modifying pathways.
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225166718