# Tumour microenvironment (TME)

Source: https://onco.cc/pathways/tumor-microenvironment/  
OnCo record `tumor-microenvironment` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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).

## Fields

- Kind: Pathway
- Last checked: 2026-09-08
- Tags: mechanism
- Analogy: 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.
- Interventions: Checkpoint blockade (PD-1, CTLA-4, LAG-3) releases exhausted T cells; Anti-VEGF normalises vessels and improves infiltration; FAP-targeted imaging and radioligands attack CAFs; CSF1R, CD47/SIRPα, CXCR4, TGF-β, adenosine (A2A/CD73) agents target myeloid and stromal suppression; most have been modest so far; Radiation and oncolytic viruses convert excluded tumours

## Notes

- Leading programmes: Tuveson (CSHL) on CAF subtypes; Sahai (Crick) and Mechta-Grigoriou (Institut Curie) on fibroblast heterogeneity; Joyce (Ludwig Lausanne) on TAMs; MD Anderson and MSK spatial atlases; Human Tumor Atlas Network (NCI).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Tumor_microenvironment
- de Visser & Joyce, The evolving tumor microenvironment (Cancer Cell 2023): https://doi.org/10.1016/j.ccell.2023.02.016
- Human Tumor Atlas Network: https://humantumoratlas.org

## Connected records

- pathways: [Cancer neuroscience (nerve-tumour signalling)](https://onco.cc/pathways/cancer-neuroscience/), [CD47 / SIRPα (the 'don't eat me' signal)](https://onco.cc/pathways/cd47-sirpa/), [Cellular senescence](https://onco.cc/pathways/senescence/), [cGAS-STING innate sensing](https://onco.cc/pathways/cgas-sting/), [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [Epithelial-mesenchymal transition & drug efflux](https://onco.cc/pathways/emt/), [Fibroblast activation, desmoplasia & matrix stiffness](https://onco.cc/pathways/caf-activation-desmoplasia/), [Hippo-YAP/TAZ](https://onco.cc/pathways/hippo-yap/), [Inflammation & NF-κB](https://onco.cc/pathways/inflammation-nfkb/), [Microbiome-tumour interactions](https://onco.cc/pathways/microbiome-tumour/), [Myeloid suppression: TAMs, MDSCs & don't-eat-me signals](https://onco.cc/pathways/myeloid-suppression-axis/), [Nutrient competition & metabolic immunosuppression](https://onco.cc/pathways/nutrient-competition-tme/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [TGF-β signalling](https://onco.cc/pathways/tgf-beta/), [The angiogenic switch & tumour vessels](https://onco.cc/pathways/angiogenic-switch/), [The metastatic cascade](https://onco.cc/pathways/metastatic-cascade/), [Theories of cancer: how the ideas connect](https://onco.cc/pathways/theories-of-cancer/), [VEGF angiogenesis](https://onco.cc/pathways/vegf-angiogenesis/)
- terms: [Angiogenesis](https://onco.cc/terms/angiogenesis/), [Cancer-associated fibroblasts (CAFs)](https://onco.cc/terms/cancer-associated-fibroblasts/), [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/), [Immune exclusion](https://onco.cc/terms/immune-exclusion/), [Immune system](https://onco.cc/terms/immune-system/), [Macrophage](https://onco.cc/terms/macrophage/), [Microenvironment and inflammation: tumours as wounds that do not heal](https://onco.cc/terms/microenvironment-inflammation-theory/), [Myeloid-derived suppressor cells (MDSCs)](https://onco.cc/terms/myeloid-derived-suppressor-cells/), [The Hodgkin microenvironment: when the cancer cell is the minority](https://onco.cc/terms/lymphoma-bio-hodgkin-microenvironment/), [Tissue organisation field theory (Sonnenschein and Soto)](https://onco.cc/terms/tissue-organisation-field-theory/), [Tumour-associated macrophages (TAMs)](https://onco.cc/terms/tumor-associated-macrophages/), [Tumour-infiltrating lymphocytes (TILs)](https://onco.cc/terms/tils/)
- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [FAPI PET](https://onco.cc/technologies/fapi-pet/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- targets: [CD30](https://onco.cc/targets/cd30/), [CD47](https://onco.cc/targets/cd47/), [CTLA-4](https://onco.cc/targets/ctla4/), [FAP](https://onco.cc/targets/fap/), [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- institutions: [Cold Spring Harbor Laboratory](https://onco.cc/institutions/cold-spring-harbor/), [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/), [Institut Curie](https://onco.cc/institutions/institut-curie/), [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- key papers: [African ancestry-associated gene expression profiles in triple-negative breast cancer underlie altered tumor biology and clinical outcome in women of African descent](https://onco.cc/key-papers/paper-martini-african-ancestry-tnbc-cancer-discov-2022/), [Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts](https://onco.cc/key-papers/paper-elyada-antigen-presenting-cafs-single-cell-cancer-discov-2019/), [Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival](https://onco.cc/key-papers/paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014/), [Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer](https://onco.cc/key-papers/paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017/), [Galon 2006: the type, density and location of immune cells in colorectal tumours predict outcome](https://onco.cc/key-papers/paper-galon-immune-contexture-colorectal-science-2006/), [Integrative analyses of colorectal cancer show Immunoscore is a stronger predictor of patient survival than microsatellite instability](https://onco.cc/key-papers/paper-mlecnik-immunoscore-msi-colorectal-immunity-2016/), [International validation of the consensus Immunoscore for the classification of colon cancer](https://onco.cc/key-papers/paper-pages-immunoscore-international-validation-lancet-2018/), [Quail and Joyce 2013: microenvironmental regulation of tumour progression and metastasis](https://onco.cc/key-papers/paper-quail-joyce-microenvironment-metastasis-natmed-2013/), [Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma](https://onco.cc/key-papers/paper-halo-301-pegvorhyaluronidase-jco-2020/), [Spatially confined sub-tumor microenvironments in pancreatic cancer](https://onco.cc/key-papers/paper-grunwald-subtme-pancreatic-cell-2021/), [Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers](https://onco.cc/key-papers/paper-gruosso-tnbc-spatial-immune-microenvironments-jci-2019/), [Stratification of pancreatic ductal adenocarcinomas based on tumor and microenvironment features](https://onco.cc/key-papers/paper-puleo-pancreatic-tumour-microenvironment-subtypes-gastroenterology-2018/), [Stromal contribution to the colorectal cancer transcriptome](https://onco.cc/key-papers/paper-isella-stromal-contribution-colorectal-transcriptome-nat-genet-2015/), [The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth](https://onco.cc/key-papers/paper-de-visser-cancer-cell/), [The tumour microenvironment in pancreatic cancer: clinical challenges and opportunities](https://onco.cc/key-papers/paper-ho-pancreatic-tumour-microenvironment-review-nrco-2020/), [Unraveling triple-negative breast cancer tumor microenvironment heterogeneity: towards an optimized treatment approach](https://onco.cc/key-papers/paper-bareche-tnbc-microenvironment-jnci-2020/), [Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)](https://onco.cc/cancers/cutaneous-t-cell-lymphoma/), [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Tenosynovial giant cell tumour (TGCT)](https://onco.cc/cancers/tenosynovial-giant-cell-tumour/)
- ideas: [What actually holds T cells at the tumour border?](https://onco.cc/ideas/idea-immune-exclusion-drivers/)

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JSON: https://onco.cc/api/v1/entities/tumor-microenvironment.json