{"entity":{"id":"paper-grunwald-subtme-pancreatic-cell-2021","kind":"paper","name":"Spatially confined sub-tumor microenvironments in pancreatic cancer","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-24","links":[{"label":"Grunwald et al., Cell 2021: spatially confined sub-tumour microenvironments","url":"https://doi.org/10.1016/j.cell.2021.09.022"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34644529/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["spatial-transcriptomics","single-cell-spatial","organoids"],"targets":[],"drugs":[],"companies":[],"institutions":["princess-margaret","oicr"],"pathways":["tumor-microenvironment","caf-activation-desmoplasia"],"terms":["desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2021,"doi":"10.1016/j.cell.2021.09.022","pmid":"34644529","authors":"Grunwald BT, Devisme A, Andrieux G, et al.","paperType":"translational","findings":["Two recurring tissue states: reactive (immune hot, aggressive) and deserted (matrix-rich, chemoprotective).","Deserted regions are enriched after chemotherapy; subTMEs arise from fibroblast differentiation trajectories."],"whatItMeans":"It explains why one biopsy can mislead and why chemotherapy selects for the protective neighbourhood, an argument for spatial rather than bulk profiling.","caveats":["Retrospective, histology-guided sampling.","No therapeutic intervention tested."],"changedPractice":false},"route":"/key-papers/paper-grunwald-subtme-pancreatic-cell-2021/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"organoids","kind":"technology","name":"Patient-derived organoids","route":"/technologies/organoids/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"},{"id":"spatial-transcriptomics","kind":"technology","name":"Spatial transcriptomics","route":"/technologies/spatial-transcriptomics/"}],"institution":[{"id":"oicr","kind":"institution","name":"Ontario Institute for Cancer Research","route":"/institutions/oicr/"},{"id":"princess-margaret","kind":"institution","name":"Princess Margaret Cancer Centre","route":"/institutions/princess-margaret/"}],"pathway":[{"id":"caf-activation-desmoplasia","kind":"pathway","name":"Fibroblast activation, desmoplasia & matrix stiffness","route":"/pathways/caf-activation-desmoplasia/"},{"id":"tumor-microenvironment","kind":"pathway","name":"Tumour microenvironment (TME)","route":"/pathways/tumor-microenvironment/"}],"term":[{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","route":"/terms/desmoplasia/"},{"id":"caf-subtypes-pancreatic","kind":"term","name":"Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF)","route":"/terms/caf-subtypes-pancreatic/"}],"journal":[{"id":"cell","kind":"journal","name":"Cell","route":"/journals/cell/"}]}}