# Immune exclusion

Source: https://onco.cc/terms/immune-exclusion/  
OnCo record `immune-exclusion` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A tumour where the immune cells arrive but are stopped at the edge, held back by scar tissue and signals such as TGF-β.

## Summary

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?

## Fields

- Kind: Term
- Last checked: 2026-09-08

## Notes

- Pancreatic ductal adenocarcinoma: T cells are absent from the regions holding cancer cells, which are coated with CXCL12 secreted by FAP-positive fibroblasts; depleting those fibroblasts or blocking CXCR4 let T cells in and uncovered the effect of anti-PD-L1 in the mouse model (Feig 2013). The long-term survivors who escape this pattern have both abundant CD8 infiltrate and high-quality neoantigens, and lose those clones at metastasis (Balachandran 2017).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Tumor_microenvironment
- Mariathasan et al., TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells (Nature 2018): https://doi.org/10.1038/nature25501

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- targets: [FAP](https://onco.cc/targets/fap/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- pathways: [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [Fibroblast activation, desmoplasia & matrix stiffness](https://onco.cc/pathways/caf-activation-desmoplasia/), [Myeloid suppression: TAMs, MDSCs & don't-eat-me signals](https://onco.cc/pathways/myeloid-suppression-axis/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [TGF-β signalling](https://onco.cc/pathways/tgf-beta/), [Tumour microenvironment (TME)](https://onco.cc/pathways/tumor-microenvironment/)
- terms: [Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF)](https://onco.cc/terms/caf-subtypes-pancreatic/), [Hallmark: avoiding immune destruction](https://onco.cc/terms/avoiding-immune-destruction/), [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Tumour-infiltrating lymphocytes (TILs)](https://onco.cc/terms/tils/)
- key papers: [Challenges and opportunities for pancreatic cancer immunotherapy](https://onco.cc/key-papers/paper-bear-pancreatic-immunotherapy-review-cancer-cell-2020/), [Genetic mechanisms of immune evasion in colorectal cancer](https://onco.cc/key-papers/paper-grasso-immune-evasion-colorectal-cancer-discov-2018/), [Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer](https://onco.cc/key-papers/paper-balachandran-neoantigen-quality-long-term-survivors-nature-2017/), [Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer](https://onco.cc/key-papers/paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013/), [TGF-beta drives immune evasion in genetically reconstituted colon cancer metastasis](https://onco.cc/key-papers/paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018/), [TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells](https://onco.cc/key-papers/paper-mariathasan-nature/)
- ideas: [What actually holds T cells at the tumour border?](https://onco.cc/ideas/idea-immune-exclusion-drivers/)

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