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A tumour is not just cancer cells. It is a neighbourhood of fibroblasts, immune cells, blood vessels, nerves, and scaffolding that the cancer recruits and corrupts, and that decides whether drugs and immune cells can get in.
Cancer-associated fibroblasts (CAFs; myCAF/iCAF/apCAF subtypes) build desmoplastic stroma and secrete TGF-β, CXCL12, and IL-6; tumour-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) suppress T cells; regulatory T cells and exhausted CD8 T cells define immune phenotypes (inflamed, excluded, desert); abnormal vasculature creates hypoxia and blocks drug delivery; extracellular matrix stiffness signals through integrins and YAP; nerves and adipocytes add fuel and signals. Single-cell and spatial profiling has turned the TME from a concept into a map with druggable niches (FAP, CSF1R, CXCR4, TGF-β, adenosine).
A castle under siege from the inside: the cancer conscripts the town's builders (fibroblasts) to raise walls, bribes the guards (macrophages) to look away, and diverts the water supply (vessels) so that reinforcements (T cells, drugs) never arrive.
One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
It replaces self-reported race with measured ancestry and shows the immune microenvironment of TNBC differs with it, a variable immunotherapy trials have not stratified on.
It explains why one biopsy can mislead and why chemotherapy selects for the protective neighbourhood, an argument for spatial rather than bulk profiling.
The definitive negative result for first-generation stromal targeting: a biomarker-selected population, a drug that did what it was designed to do to the matrix, and no survival benefit; the stroma ideas on this page start from here.
The reference for why pancreatic microenvironment trials read as a list of failures and what the field now means by remodelling rather than removing the stroma.
It links the Lehmann subtypes to the spatial immune classes of Gruosso and gives a rationale for pairing checkpoint inhibitors with the immunomodulatory subtype and stromal or metabolic agents with the cold ones.
Fibroblasts are part of the immune conversation, not just a physical barrier, which is why stromal and immune strategies are now designed together.
It explains why a PD-L1 score alone predicts imperfectly: PD-L1 on stromal cells with excluded T cells is a poor-outcome pattern, and B7-H4 marks the cold tumours now being targeted by antibody-drug conjugates.
Shares Unraveling triple-negative breast cancer tumor microenvironment heterogeneity: towards an optimized treatment approach, CD47 / SIRPα (the 'don't eat me' signal), Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts, Integrative analyses of colorectal cancer show Immunoscore is a stronger predictor of patient survival than microsatellite instability and the tag mechanism.
Shares Myeloid-derived suppressor cells (MDSCs), Myeloid suppression: TAMs, MDSCs & don't-eat-me signals, Fibroblast activation, desmoplasia & matrix stiffness, Inflammation & NF-κB and the tag mechanism.
Shares Tumour-associated macrophages (TAMs), CD47, Cold Spring Harbor Laboratory, Myeloid suppression: TAMs, MDSCs & don't-eat-me signals and the tag mechanism.
Shares cGAS-STING innate sensing, Theories of cancer: how the ideas connect, Single-cell & spatial profiling, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares Cold Spring Harbor Laboratory, Inflammation & NF-κB, MD Anderson Cancer Center, Pancreatic ductal adenocarcinoma and the tag mechanism.
Shares Cold Spring Harbor Laboratory, The metastatic cascade, TGF-β signalling, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares Nutrient competition & metabolic immunosuppression, Theories of cancer: how the ideas connect, MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares Theories of cancer: how the ideas connect, Inflammation & NF-κB, Dana-Farber Brigham Cancer Center, Memorial Sloan Kettering Cancer Center and the tag mechanism.