Comprehensive single-cell pan-cancer atlas unveils IFI30+ macrophages as key modulators of intra-tumoral immune dynamics

Background The convergence of macrophage-targeted strategies with immune checkpoint blockade therapies defines a pivotal avenue in contemporary tumor therapy. Identifying robust genetic regulators in this context is imperative. Methods This study elucidates IFI30's role in enhancing Major Histocompatibility Complex II (MHC-II) restriction antigen processing. Despite its recognition in cancer immunotherapy, IFI30 remains a nascent focus. Our approach involves a multi-omics analysis of IFI30 tumor immunological profile in the macrophage-mediated Tumor Microenvironment (TME), spanning various cancers and bolstered by rigorous co-culture laboratory work. Results IFI30 predominantly localizes in monocyte/macrophage populations, correlating strongly with immune cell infiltration. Substantiated by single-cell analysis, IFI30 exhibits significant functional enrichment in immune-related pathways. Co-expression with immune-related genes, including MHC elements and immune checkpoints, further validates its relevance. Conclusion Our study positions IFI30 as a promising immunotherapeutic target. Pan-cancer analyses and glioblastoma multiforme (GBM) investigations collectively underscore IFI30's potential as a TME modulator, particularly in its interaction with M2-macrophages. IFI30 emerges as a prospective intervention point in the immunotherapeutic landscape.