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Spatial and multi-omic profiling reveals genes and pathways associated with cytotoxic lymphocyte infiltration in malignant rhabdoid tumor

Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers with poor outcomes. MRTs exhibit low tumor mutational burden, yet recent studies reported immune cell infiltration. Here, we used spatial transcriptomics and multi-omics to explore molecular and cellular features associated with immune cell infiltration in MRT. We identified a diverse set of tumor antigens (TAs) expressed by MRT cells and showed that genes associated with the IRF1 signaling pathway and antigen processing/presentation are significantly correlated with cytotoxic lymphocyte infiltration. A subset of MRTs with high CD8+ T cell infiltration also exhibited increased expression of a skeletal muscle developmental program. Additionally, we found that the M1/M2 macrophage ratio strongly correlated with cytotoxic lymphocyte infiltration and identified genes and regulatory networks that potentially play roles in M2-like tumor-associated macrophages.