ImmunoFusion: A Unified Platform for Investigating RNA-seq-Derived Gene Fusions in Cancer and Immunotherapy

Abstract

BackgroundGene fusions play a critical role in cancer development by persistently activating kinases or inactivating tumor suppressor genes, leading to altered signal transduction and gene expression regulation. However, their impact on treatment responses remains poorly understood. Although existing cancer databases catalog numerous fusion events or immune checkpoint blockade (ICB) studies, no unified platform integrates gene fusion data across cancer types while linking them to the tumor microenvironment (TME) and patient outcomes. Such integration is essential for elucidating how fusions shape immune responses and for developing improved biomarkers for personalized cancer therapies. MethodsTo address this gap, we constructed the Fusion Immune Atlas (ImmunoFusion), a platform integrating data from TCGA, TARGET, CPTAC, and 29 ICB cohorts (including ICB treatments and other treatment modalities) across diverse cancer types. We identified fusion events from raw RNA-seq data using Arriba and STAR-Fusion, and standardized fusion calls by adapting MetaFusion to the GRCh38 reference genome. Additionally, we curated clinical data and estimated TME signatures and cell fractions using the Immuno-Oncology Biological Research (IOBR) approach. ImmunoFusion was developed using the high-quality Rhino framework for Shiny applications, built on R. ResultsImmunoFusion (https://shiny.zhoulab.ac.cn/ImmunoFusion) encompasses 21,014 clinical samples, serving as a comprehensive RNA-seq-derived gene fusion database and analytical tool. It offers functionalities to investigate fusion breakpoints, confidence scores, frequency patterns, and associations with clinical variables. The platform also enables TME evaluation and interactive exploration of fusions for analyzing tumor immunophenotypes in cancer and immunotherapy contexts. As an illustration, analysis of MTAP fusions in lung cancer cohorts revealed their association with a metabolically depleted, "cold" (immune-suppressive) tumor environment and poorer patient outcomes, pinpointing MTAP fusions as a novel biomarker for treatment selection. ConclusionsImmunoFusion represents a significant advancement, delivering a unified platform to explore the influence of gene fusions on cancer and immune responses. It offers particular value in understanding fusion-driven immunotherapy outcomes, paving the way for more effective therapeutic strategies.