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Mapping pancreatic tumours region by region found that the tissue organises itself into two recurring neighbourhoods: reactive ones full of active fibroblasts and immune cells beside aggressive tumour cells, and deserted matrix-rich ones that protect the cancer from chemotherapy.
The human pancreatic tumour microenvironment was deconvoluted through large-scale integration of histology-guided regional multi-omics with clinical data and patient-derived preclinical models. Histologically definable tissue states anchored in fibroblast plasticity, termed subTMEs, showed regional relationships to tumour immunity, subtypes, differentiation and treatment response. Reactive subTMEs rich in coordinated fibroblast communities were immune hot and inhabited by aggressive tumour phenotypes; matrix-rich deserted subTMEs had fewer activated fibroblasts and tumour-suppressive features yet were markedly chemoprotective and enriched after chemotherapy. SubTMEs originated in fibroblast differentiation trajectories, and their intratumoural co-occurrence produced patient-specific, computationally predictable heterogeneity.
It explains why one biopsy can mislead and why chemotherapy selects for the protective neighbourhood, an argument for spatial rather than bulk profiling.
Shares Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF), Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME).
Shares Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF), Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME), Single-cell & spatial profiling.
Shares Ontario Institute for Cancer Research, Princess Margaret Cancer Centre, Single-cell & spatial profiling.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Single-cell & spatial profiling, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME), Pancreatic ductal adenocarcinoma.
Shares Ontario Institute for Cancer Research, Princess Margaret Cancer Centre.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME), Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.