Spatial epitope barcoding reveals clonal tumor patch behaviors
Menée à l'aide de modèles de xénogreffes de cancer du poumon à petites cellules, cette étude présente un système de marquage cellulaire couplé à la technologie d'imagerie par faisceau d'ions multiplexés pour suivre le comportement des cellules dans la tumeur et met en évidence l'expansion préférentielle de certains sous-types cellulaires
Intratumoral heterogeneity is a seminal feature of human tumors contributing to tumor progression and response to treatment. Current technologies are still largely unsuitable to accurately track phenotypes and clonal evolution within tumors, especially in response to genetic manipulations. Here, we developed epitopes for imaging using combinatorial tagging (EpicTags), which we coupled to multiplexed ion beam imaging (EpicMIBI) for in situ tracking of barcodes within tissue microenvironments. Using EpicMIBI, we dissected the spatial component of cell lineages and phenotypes in xenograft models of small cell lung cancer. We observed emergent properties from mixed clones leading to the preferential expansion of clonal patches for both neuroendocrine and non-neuroendocrine cancer cell states in these models. In a tumor model harboring a fraction of PTEN-deficient cancer cells, we observed a non-autonomous increase of clonal patch size in PTEN wild-type cancer cells. EpicMIBI facilitates in situ interrogation of cell-intrinsic and cell-extrinsic processes involved in intratumoral heterogeneity.
Cancer Cell 2022