Spatially resolved analysis of pancreatic cancer identifies therapy-associated remodeling of the tumor microenvironment.

ABSTRACT: In combination with cell-intrinsic properties, interactions in the tumor microenvironment modulate therapeutic response. We leveraged single-cell spatial transcriptomics to dissect the remodeling of multicellular neighborhoods and cell-cell interactions in human pancreatic cancer associated with neoadjuvant chemotherapy and radiotherapy. We developed spatially constrained optimal transport interaction analysis (SCOTIA), an optimal transport model with a cost function that includes both spatial distance and ligand-receptor gene expression. Our results uncovered a marked change in ligand-receptor interactions between cancer-associated fibroblasts and malignant cells in response to treatment, which was supported by orthogonal datasets, including an ex vivo tumoroid coculture system. We identi

SUBMITTER: Shiau C 

PROVIDER: S-EPMC11816915 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature