Immune cell landscape and metabolic gene activity distinguish triple negative from luminal A-like ductal carcinoma in situ

Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer, and up to 50% of the lesions remain non-invasive even if untreated. Both tumor and microenvironmental features are associated with disease progression, but the cellular interactions are poorly understood. We investigated DCIS of the clinical breast cancer subtypes; Triple Negative (TN) and Luminal A (LumA)-like, presumed to represent lesions with the most contrasting invasive potential, using spatial transcriptomic and multiplex immunofluorescence analyses. In the intraductal cancer cells, we found significant differences between the two subtypes in expression of genes related to energy metabolism and secreted proteins. In the periductal space, we found differences in the absolute density of CD4 + T cells, CD8 + T cells, and B cells between TN and LumA-like DCIS. Spatial cellular neighborhood analyses revealed an inverse relationship between CD4 + T cells and B cells. These data suggest specific biological properties of TN and LumA-like DCIS that might underpin differences in progression potential.