Analisi a cellula singola della ristrutturazione indotta dalla chemioterapia rivela una resistenza chimioterapica basale guidata da CD276 nel cancro pancreatico.

BACKGROUND & AIMS: Unresectable advanced pancreatic ductal adenocarcinoma (PDAC) typically requires systematic chemotherapy, but it remains unclear how this treatment remodels tumor cell plasticity and the tumor microenvironment (TME) to influence clinical outcomes. METHODS: We conducted single-cell RNA sequencing on paired pre- and posttreatment tumor biopsies and peripheral blood mononuclear cells from 28 patients with PDAC receiving abraxane plus gemcitabine chemotherapy. To validate the chemoresistant niche, we employed multiplex immunofluorescence and spatial transcriptomics, ranging from in situ sequencing to 10X Visium HD at 2-μm resolution. In addition, we performed functional valid