Background: Sarcomatoid renal cell carcinoma (RCC) is thought to arise from an epithelial to mesenchymal transition (EMT) of the parental tumor, most commonly clear cell RCC. These tumors are known to be highly immunogenic. Whether the EMT state impacts the immune milieu and responsiveness to immunotherapy, is unknown. This study explores the capacity of spatial molecular imaging (SMI) to dissect the tumor immune microenvironment (TiME) and EMT in sarcomatoid RCC.
Methods: Nanostring’s SMI platform, CosMx, was used to spatially capture single cell level transcriptomic data in two sarcomatoid RCC specimens, one from a responder to immunotherapy and one from a non-responder. Fields of view within sarcomatoid, clear cell, and transition areas were selected using H&E and further segmented with morphology markers SYTO11, PanCK, CD3, and CD45. We compared regions within each tumor and the two specimens.
Results: Forty fields of view and over 100,000 single cells were captured. Epithelial staining was high in clear cell regions and decreased to near absent in the sarcomatoid regions. Distinct tumor cell clusters and differing immune cell types existed between clear cell and sarcomatoid areas. Clustering revealed shared tumor cell populations between the responder and non-responder as well as unique populations in each. In the sarcomatoid regions, immune infiltrate was dispersed in the non-responder, but clustered in perivascular regions in the responder. CD4+ naïve T cells and myeloid dendritic cells were higher in the responder while CD4+ memory cells, CD8+ naïve T cells, and plasmacytoid dendritic cells were more abundant in the non-responder.
Conclusions: We identified differences in the TiME between the responder and non-responder tumors that could contribute to immunotherapy responsiveness. Although no conclusions can be drawn due to the limited sample number, these data demonstrate the power of SMI to detect single cell level differences in sarcomatoid RCC in spatial relation to histology and the TiME.