{"entity":{"id":"immune-exclusion","kind":"term","name":"Immune exclusion","aka":[],"tldr":"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?","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Tumor_microenvironment","links":[{"label":"Mariathasan et al., TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells (Nature 2018)","url":"https://doi.org/10.1038/nature25501"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["fap","vegf","cxcr3"],"drugs":["retlirafusp-alfa","ficerafusp-alfa"],"companies":[],"institutions":[],"pathways":["tgf-beta","tumor-microenvironment","pd1-checkpoint"],"terms":["cold-vs-hot","tils"],"trials":["fortifi-hn01","nct04950322","nct05300269","nct05503888","nct05671822","nct06679673","nct07102901","nct07175220","nct07478731","nct07503639","nct07728019","nct07752550","nct07773363","nct07797244","nct07802184","nct07807163","nct07814859","nct07815288"],"people":[],"bottlenecks":[],"keyPapers":["paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013","paper-balachandran-neoantigen-quality-long-term-survivors-nature-2017","paper-mariathasan-nature"],"journals":[],"dependsOn":[],"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)."],"category":"Cancer biology"},"route":"/terms/immune-exclusion/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"target":[{"id":"cxcr3","kind":"target","name":"CXCR3","route":"/targets/cxcr3/"},{"id":"fap","kind":"target","name":"FAP","route":"/targets/fap/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"drug":[{"id":"ficerafusp-alfa","kind":"drug","name":"Ficerafusp alfa","route":"/drugs/ficerafusp-alfa/"},{"id":"retlirafusp-alfa","kind":"drug","name":"Retlirafusp alfa","route":"/drugs/retlirafusp-alfa/"}],"pathway":[{"id":"immune-desert-exclusion","kind":"pathway","name":"Cold tumours: immune deserts and exclusion","route":"/pathways/immune-desert-exclusion/"},{"id":"caf-activation-desmoplasia","kind":"pathway","name":"Fibroblast activation, desmoplasia & matrix stiffness","route":"/pathways/caf-activation-desmoplasia/"},{"id":"myeloid-suppression-axis","kind":"pathway","name":"Myeloid suppression: TAMs, MDSCs & don't-eat-me signals","route":"/pathways/myeloid-suppression-axis/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"},{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"},{"id":"tumor-microenvironment","kind":"pathway","name":"Tumour microenvironment (TME)","route":"/pathways/tumor-microenvironment/"}],"term":[{"id":"caf-subtypes-pancreatic","kind":"term","name":"Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF)","route":"/terms/caf-subtypes-pancreatic/"},{"id":"avoiding-immune-destruction","kind":"term","name":"Hallmark: avoiding immune destruction","route":"/terms/avoiding-immune-destruction/"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"tils","kind":"term","name":"Tumour-infiltrating lymphocytes (TILs)","route":"/terms/tils/"}],"trial":[{"id":"nct07797244","kind":"trial","name":"A Single-Arm, Phase II Study of Retlirafusp Alfa in Combination With XELOX and Bevacizumab for the First-Line Treatment of Advanced RAS-Mutated Colorectal Cance","route":"/trials/nct07797244/"},{"id":"nct07807163","kind":"trial","name":"A Study Evaluating Ficerafusp Alfa (BCA101) QW in Combination With Pembrolizumab vs Alternative Ficerafusp Alfa Dosing in 1L R or M HNSCC","route":"/trials/nct07807163/"},{"id":"nct04950322","kind":"trial","name":"A Trial of SHR1701 Plus Chemotherapy in Patients With Gastric or Gastroesophageal Cancer","route":"/trials/nct04950322/"},{"id":"nct07728019","kind":"trial","name":"Efficacy and Safety of Retlirafusp Alfa Plus Bevacizumab and Chemotherapy With or Without Short-Course Radiotherapy in Patients With CRCLM","route":"/trials/nct07728019/"},{"id":"fortifi-hn01","kind":"trial","name":"FORTIFI-HN01","route":"/trials/fortifi-hn01/"},{"id":"nct07802184","kind":"trial","name":"GnP Combined With SHR-1701 and Apatinib as First-Line Treatment for Locally Advanced or Metastatic PDAC","route":"/trials/nct07802184/"},{"id":"nct07478731","kind":"trial","name":"Neoadjuvant SHR-1701 Plus Chemoradiotherapy for Locally Advanced Rectal Cancer","route":"/trials/nct07478731/"},{"id":"nct05671822","kind":"trial","name":"Ph1b/2 Study of the Safety and Efficacy of SHR-A1811 Combinations in Advanced HER2 Expression Gastric Cancer","route":"/trials/nct05671822/"},{"id":"nct05503888","kind":"trial","name":"Phase Ib/II Study of Almonertinib Combined With SHR-1701 in the Treatment of Relapsed or Advanced Non-small Cell Lung Cancer","route":"/trials/nct05503888/"},{"id":"nct07175220","kind":"trial","name":"Phase II Clinical Study of SHR2554 Tablets Combined With Other Anti-tumor Treatments in Non-small Cell Lung Cancer Subjects","route":"/trials/nct07175220/"},{"id":"nct07752550","kind":"trial","name":"Retlirafusp Alfa Combined With Chemotherapy or Fuzuloparib for Triple-Negative Breast Cancer","route":"/trials/nct07752550/"},{"id":"nct07814859","kind":"trial","name":"Retlirafusp Alfa Combined With Famitinib, Nab-Paclitaxel and Gemcitabine for First-Line Treatment of Patients With Unresectable Pancreatic Cancer","route":"/trials/nct07814859/"},{"id":"nct07773363","kind":"trial","name":"Retlirafusp Alfa Plus Apatinib and Chemotherapy as Second-Line Treatment for Pancreatic Cancer","route":"/trials/nct07773363/"},{"id":"nct07815288","kind":"trial","name":"Retlirafusp Alfa Plus Targeted Therapy and Chemotherapy for Unresectable Colorectal Liver-Limited Metastases","route":"/trials/nct07815288/"},{"id":"nct07102901","kind":"trial","name":"Safety and Efficacy of SHR2554 Combined With Other Antitumor Therapies in Gastric or Gastro-oesophageal Junction Adenocarcinoma","route":"/trials/nct07102901/"},{"id":"nct06679673","kind":"trial","name":"SHR-1701 Combined with SHR2554 and BP102 for MCRC","route":"/trials/nct06679673/"},{"id":"nct05300269","kind":"trial","name":"SHR-1701 in Combination With Chemotherapy and Radiotherapy in Locally Advanced Rectal Cancer","route":"/trials/nct05300269/"},{"id":"nct07503639","kind":"trial","name":"Umbrella Trial of Neoadjuvant Therapy for Locally Advanced Colorectal Cancer","route":"/trials/nct07503639/"}],"paper":[{"id":"paper-bear-pancreatic-immunotherapy-review-cancer-cell-2020","kind":"paper","name":"Challenges and opportunities for pancreatic cancer immunotherapy","route":"/key-papers/paper-bear-pancreatic-immunotherapy-review-cancer-cell-2020/"},{"id":"paper-grasso-immune-evasion-colorectal-cancer-discov-2018","kind":"paper","name":"Genetic mechanisms of immune evasion in colorectal cancer","route":"/key-papers/paper-grasso-immune-evasion-colorectal-cancer-discov-2018/"},{"id":"paper-balachandran-neoantigen-quality-long-term-survivors-nature-2017","kind":"paper","name":"Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer","route":"/key-papers/paper-balachandran-neoantigen-quality-long-term-survivors-nature-2017/"},{"id":"paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013","kind":"paper","name":"Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer","route":"/key-papers/paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013/"},{"id":"paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018","kind":"paper","name":"TGF-beta drives immune evasion in genetically reconstituted colon cancer metastasis","route":"/key-papers/paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018/"},{"id":"paper-mariathasan-nature","kind":"paper","name":"TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells","route":"/key-papers/paper-mariathasan-nature/"}],"idea":[{"id":"idea-immune-exclusion-drivers","kind":"idea","name":"What actually holds T cells at the tumour border?","route":"/ideas/idea-immune-exclusion-drivers/"}]}}