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-omic profiling to study immune cell infiltration in MRT samples. We observed a diverse repertoire of candidate tumor antigens (TAs), IRF1 signaling activity and elevated expression of antigen processing and presentation genes, strongly associated with a "hot" tumor immune microenvironment (TIME). Upregulation of factors involved in skeletal muscle development was observed in some MRTs with higher CD8 + T cell infiltration and the ratio of M1/M2 macrophages was positively correlated with cytotoxic lymphocyte infiltration. We identified genes, such as SPP1 , preferentially expressed in tumor-associated macrophages (TAMs) and noted the MITF regulatory network appeared active in the M2-like TAMs.