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A tumour where the immune cells arrive but are stopped at the edge, held back by scar tissue and signals such as TGF-β.
Immune exclusion describes a tumour where immune cells arrive but are stopped at the edge, held back by scar tissue and signals such as TGF-β. It is one of three immune phenotypes (inflamed, excluded and desert) and is associated with TGF-β-activated fibroblasts, dense extracellular matrix and abnormal vessels, as described in the TGF-β signalling and Tumour microenvironment (TME) pathways and the Hot vs cold tumours entry. It predicts poor response to checkpoint inhibitors in bladder, colorectal and pancreatic cancer, and the candidate targets are TGF-β, FAP, CXCL12/CXCR4 and VEGF / VEGFR. Readers meet the term in the hallmark Avoiding immune destruction, in the cold tumours pathway, and in the idea What actually holds T cells at the tumour border?
In plain words · FAP (fibroblast activation protein) sits on the cancer-associated fibroblasts that scaffold more than 90% of epithelial cancers and is almost absent from normal adult tissue. FAPI PET tracers therefore light up tumours with high contrast, including pancreatic, gastric and low-grade cancers where FDG PET is weak, and FAP-targeted radioligands are in development.
Showing the target this term concerns: FAP.
The clearest statement of why the corpus records so many negative immunotherapy trials here, and of the design logic behind the vaccine and agonist combinations now in trials.
It gives a genetic account of both immunotherapy failures: why some mismatch repair deficient tumours resist, and why the microsatellite-stable majority has no T cells in it to begin with.
It is the clearest mechanistic answer to why microsatellite-stable colorectal cancer resists immunotherapy, and the rationale for every TGF-beta plus checkpoint combination now in trials in this disease.
One term page and one idea page on OnCo cite 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 pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
It is the proof that T cells can control pancreatic cancer in some people, and the scientific basis for the personalised neoantigen vaccines now in trials.
The mechanistic account of T-cell exclusion that all later combination immunotherapy trials in pancreatic cancer cite, and the origin of CXCR4 inhibitor combinations.
Shares Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF), FAP, Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME).
Shares Myeloid suppression: TAMs, MDSCs & don't-eat-me signals, Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME), Hot vs cold tumours.
Shares Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF), Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME), Pancreatic ductal adenocarcinoma.
Shares TGF-beta drives immune evasion in genetically reconstituted colon cancer metastasis, TGF-β signalling, Cold tumours: immune deserts and exclusion, Colorectal cancer.
Shares Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF), Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME), Pancreatic ductal adenocarcinoma.
Shares FAP, Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME), Hot vs cold tumours.
Shares Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF), FAP, TGF-β signalling, Cold tumours: immune deserts and exclusion.
Shares Cold tumours: immune deserts and exclusion, Hot vs cold tumours, PD-1 / PD-L1 immune checkpoint & T-cell activation, Colorectal cancer.