{"entity":{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","aka":[],"tldr":"'Hot' tumours are full of immune cells and respond to immunotherapy; 'cold' tumours have kept the immune system out.","summary":"Hot tumours are full of immune cells and tend to respond to immunotherapy, whereas cold tumours have kept the immune system out. Immunologists distinguish inflamed tumours, immune-excluded tumours in which T cells are held at the margin by TGF-β and stroma, and immune deserts. Pancreatic cancer, prostate cancer, glioblastoma and most HR-positive breast cancers are cold, and turning cold tumours hot is the goal of radiation, vaccines, ISACs, STING agonists and oncolytic viruses. The term is linked to the Immune checkpoint inhibitors, STING & innate immune agonists and Oncolytic viruses technologies and to Desmoplasia (tumour stroma), and it is referenced by the Pancreatic ductal adenocarcinoma and Glioma & glioblastoma entries, Miriam Merad and the bottleneck on cold tumours.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tumor_microenvironment","links":[{"label":"NCI Dictionary of Cancer Terms: hot tumor","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hot-tumor"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["checkpoint-inhibitor","sting-agonist","oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013","paper-royal-ipilimumab-pancreatic-j-immunother-2010","paper-brahmer-anti-pd-l1-phase-1-nejm-2012","paper-oreilly-durvalumab-tremelimumab-pancreatic-jama-oncol-2019","paper-bear-pancreatic-immunotherapy-review-cancer-cell-2020"],"journals":[],"dependsOn":[],"notes":["Pancreatic ductal adenocarcinoma is the archetypal cold tumour: T cells exist but are held at the margin by CXCL12 from FAP-positive fibroblasts (Feig 2013) and MHC class I is degraded by autophagy (Yamamoto 2020), so single-agent ipilimumab (0 of 27), anti-PD-L1 (0 of 14 pancreatic patients) and durvalumab with or without tremelimumab (3.1% and 0% of 65) all failed; the only responsive group is the 1 to 2% with mismatch repair deficiency (Royal 2010, Brahmer 2012, O'Reilly 2019, Bear 2020)."],"category":"Immunology"},"route":"/terms/cold-vs-hot/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"dietary-fibre-microbiome-io","kind":"technology","name":"Dietary fibre and the gut microbiome for immunotherapy response","route":"/technologies/dietary-fibre-microbiome-io/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"microbiome-modulation-io","kind":"technology","name":"Microbiome modulation to unlock immunotherapy","route":"/technologies/microbiome-modulation-io/"},{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"},{"id":"spatial-omics-guided-therapy","kind":"technology","name":"Spatial-omics-guided treatment selection","route":"/technologies/spatial-omics-guided-therapy/"},{"id":"sting-agonist","kind":"technology","name":"STING & innate immune agonists","route":"/technologies/sting-agonist/"}],"paper":[{"id":"paper-ricciuti-tmb-pd-l1-levels-jama-oncol-2022","kind":"paper","name":"Association of high tumor mutation burden in non-small cell lung cancers with increased immune infiltration and improved clinical outcomes of PD-L1 blockade across PD-L1 expression levels","route":"/key-papers/paper-ricciuti-tmb-pd-l1-levels-jama-oncol-2022/"},{"id":"paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019","kind":"paper","name":"Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370)","route":"/key-papers/paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019/"},{"id":"paper-yamamoto-nature","kind":"paper","name":"Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I","route":"/key-papers/paper-yamamoto-nature/"},{"id":"paper-binnewies-tumor-immune-microenvironment-natmed-2018","kind":"paper","name":"Binnewies 2018: understanding the tumour immune microenvironment for effective therapy","route":"/key-papers/paper-binnewies-tumor-immune-microenvironment-natmed-2018/"},{"id":"paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024","kind":"paper","name":"Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial","route":"/key-papers/paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024/"},{"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-chen-mellman-cancer-immunity-cycle-immunity-2013","kind":"paper","name":"Chen and Mellman 2013: the cancer-immunity cycle","route":"/key-papers/paper-chen-mellman-cancer-immunity-cycle-immunity-2013/"},{"id":"paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015","kind":"paper","name":"Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities","route":"/key-papers/paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015/"},{"id":"paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014","kind":"paper","name":"Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival","route":"/key-papers/paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014/"},{"id":"paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022","kind":"paper","name":"Diminished efficacy of programmed death-(ligand)1 inhibition in STK11- and KEAP1-mutant lung adenocarcinoma is affected by KRAS mutation status","route":"/key-papers/paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022/"},{"id":"paper-oreilly-durvalumab-tremelimumab-pancreatic-jama-oncol-2019","kind":"paper","name":"Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical trial","route":"/key-papers/paper-oreilly-durvalumab-tremelimumab-pancreatic-jama-oncol-2019/"},{"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-keynote-189-nejm-2018","kind":"paper","name":"KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation","route":"/key-papers/paper-keynote-189-nejm-2018/"},{"id":"paper-gay-sclc-subtypes-inflamed-cancer-cell-2021","kind":"paper","name":"Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities","route":"/key-papers/paper-gay-sclc-subtypes-inflamed-cancer-cell-2021/"},{"id":"paper-royal-ipilimumab-pancreatic-j-immunother-2010","kind":"paper","name":"Phase 2 trial of single agent ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma","route":"/key-papers/paper-royal-ipilimumab-pancreatic-j-immunother-2010/"},{"id":"paper-sethna-rna-neoantigen-vaccine-long-lived-t-cells-nature-2025","kind":"paper","name":"RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer","route":"/key-papers/paper-sethna-rna-neoantigen-vaccine-long-lived-t-cells-nature-2025/"},{"id":"paper-brahmer-anti-pd-l1-phase-1-nejm-2012","kind":"paper","name":"Safety and activity of anti-PD-L1 antibody in patients with advanced cancer","route":"/key-papers/paper-brahmer-anti-pd-l1-phase-1-nejm-2012/"},{"id":"paper-kras-nsclc-cancer-discov-2018","kind":"paper","name":"STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma","route":"/key-papers/paper-kras-nsclc-cancer-discov-2018/"},{"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-ho-pancreatic-tumour-microenvironment-review-nrco-2020","kind":"paper","name":"The tumour microenvironment in pancreatic cancer: clinical challenges and opportunities","route":"/key-papers/paper-ho-pancreatic-tumour-microenvironment-review-nrco-2020/"}],"term":[{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","route":"/terms/desmoplasia/"},{"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":"immune-checkpoint","kind":"term","name":"Immune checkpoint","route":"/terms/immune-checkpoint/"},{"id":"immune-exclusion","kind":"term","name":"Immune exclusion","route":"/terms/immune-exclusion/"},{"id":"immune-surveillance-immunoediting","kind":"term","name":"Immune surveillance and cancer immunoediting","route":"/terms/immune-surveillance-immunoediting/"},{"id":"immune-system","kind":"term","name":"Immune system","route":"/terms/immune-system/"},{"id":"immuno-oncology","kind":"term","name":"Immuno-oncology (IO) and checkpoint blockade","route":"/terms/immuno-oncology/"},{"id":"immunotherapy-term","kind":"term","name":"Immunotherapy","route":"/terms/immunotherapy-term/"},{"id":"inflammation","kind":"term","name":"Inflammation","route":"/terms/inflammation/"},{"id":"microenvironment-inflammation-theory","kind":"term","name":"Microenvironment and inflammation: tumours as wounds that do not heal","route":"/terms/microenvironment-inflammation-theory/"},{"id":"mss-pmmr","kind":"term","name":"Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)","route":"/terms/mss-pmmr/"},{"id":"pancreatic-failed-programmes","kind":"term","name":"Pancreatic cancer: the failed and stopped programmes and why","route":"/terms/pancreatic-failed-programmes/"},{"id":"stk11-keap1","kind":"term","name":"STK11 / KEAP1 co-mutations","route":"/terms/stk11-keap1/"},{"id":"t-cell-exhaustion-term","kind":"term","name":"T-cell exhaustion and CAR-T persistence","route":"/terms/t-cell-exhaustion-term/"}],"trial":[{"id":"nct05608044","kind":"trial","name":"A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer","route":"/trials/nct05608044/"},{"id":"autogene-cevumeran-phase-1","kind":"trial","name":"Autogene cevumeran phase 1 in resected pancreatic cancer (Memorial Sloan Kettering)","route":"/trials/autogene-cevumeran-phase-1/"},{"id":"checkmate-142","kind":"trial","name":"CheckMate 142","route":"/trials/checkmate-142/"},{"id":"checkmate-143","kind":"trial","name":"CheckMate 143","route":"/trials/checkmate-143/"},{"id":"checkmate-498","kind":"trial","name":"CheckMate 498","route":"/trials/checkmate-498/"},{"id":"checkmate-548","kind":"trial","name":"CheckMate 548","route":"/trials/checkmate-548/"},{"id":"eclipse","kind":"trial","name":"ECLIPSE (GVAX pancreas and CRS-207)","route":"/trials/eclipse/"},{"id":"imblaze370","kind":"trial","name":"IMblaze370","route":"/trials/imblaze370/"},{"id":"sequoia","kind":"trial","name":"SEQUOIA","route":"/trials/sequoia/"}],"idea":[{"id":"idea-bio2-tumour-anchored-tgfbeta-trap","kind":"idea","name":"Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhere","route":"/ideas/idea-bio2-tumour-anchored-tgfbeta-trap/"},{"id":"idea-bio2-myeloid-engager-bispecific","kind":"idea","name":"Bispecific antibodies that engage macrophages instead of T cells","route":"/ideas/idea-bio2-myeloid-engager-bispecific/"},{"id":"idea-bio2-complement-c5ar-blockade","kind":"idea","name":"Block the complement signal that recruits tumour-protecting cells","route":"/ideas/idea-bio2-complement-c5ar-blockade/"},{"id":"idea-bio2-cxcr2-neutrophil-blockade","kind":"idea","name":"Clear the suppressive neutrophils out of pancreatic tumours first","route":"/ideas/idea-bio2-cxcr2-neutrophil-blockade/"},{"id":"idea-bio2-lactate-acid-axis","kind":"idea","name":"De-acidify the tumour so T cells can work in it","route":"/ideas/idea-bio2-lactate-acid-axis/"},{"id":"idea-bio2-tertiary-lymphoid-induction","kind":"idea","name":"Grow immune command posts inside tumours","route":"/ideas/idea-bio2-tertiary-lymphoid-induction/"},{"id":"idea-bio1-organoid-immune-coculture","kind":"idea","name":"Grow tumour organoids together with the patient's own immune cells","route":"/ideas/idea-bio1-organoid-immune-coculture/"},{"id":"idea-moon-cold-to-hot-programme","kind":"idea","name":"Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours","route":"/ideas/idea-moon-cold-to-hot-programme/"},{"id":"idea-immunotherapy-mss-crc","kind":"idea","name":"Making microsatellite-stable colorectal cancer immunotherapy-responsive","route":"/ideas/idea-immunotherapy-mss-crc/"},{"id":"idea-bio1-spatial-clone-immune-map","kind":"idea","name":"Map which tumour clones sit next to which immune cells before choosing therapy","route":"/ideas/idea-bio1-spatial-clone-immune-map/"},{"id":"idea-neoadjuvant-io-glioblastoma","kind":"idea","name":"Neoadjuvant immunotherapy with surgical window for glioblastoma","route":"/ideas/idea-neoadjuvant-io-glioblastoma/"},{"id":"idea-bio2-trem2-myeloid-reprogramming","kind":"idea","name":"Reprogramme suppressive macrophages instead of trying to delete them","route":"/ideas/idea-bio2-trem2-myeloid-reprogramming/"},{"id":"idea-pdac-stromal-reprogramming-not-depletion","kind":"idea","name":"Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival 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others","route":"/ideas/idea-bio2-in-situ-vaccination-solid/"},{"id":"idea-bio2-spatial-signature-cdx","kind":"idea","name":"Turn the map of immune cells inside a tumour into a standardised test","route":"/ideas/idea-bio2-spatial-signature-cdx/"},{"id":"idea-bio2-epigenetic-priming-cold-tumours","kind":"idea","name":"Unmask hidden antigens with a short epigenetic course before immunotherapy","route":"/ideas/idea-bio2-epigenetic-priming-cold-tumours/"},{"id":"idea-immune-exclusion-drivers","kind":"idea","name":"What actually holds T cells at the tumour border?","route":"/ideas/idea-immune-exclusion-drivers/"}],"drug":[{"id":"pegilodecakin","kind":"drug","name":"Pegilodecakin","route":"/drugs/pegilodecakin/"}],"biomarker":[{"id":"stk11-keap1-loss","kind":"biomarker","name":"STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma","route":"/biomarkers/stk11-keap1-loss/"}],"roadmap":[{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/"}],"person":[{"id":"miriam-merad","kind":"person","name":"Miriam Merad","route":"/people/miriam-merad/"},{"id":"pawel-kalinski","kind":"person","name":"Pawel Kalinski","route":"/people/pawel-kalinski/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"},{"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":"nutrient-competition-tme","kind":"pathway","name":"Nutrient competition & metabolic immunosuppression","route":"/pathways/nutrient-competition-tme/"},{"id":"t-cell-exhaustion","kind":"pathway","name":"T-cell exhaustion","route":"/pathways/t-cell-exhaustion/"},{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"},{"id":"cancer-immunity-cycle","kind":"pathway","name":"The cancer-immunity cycle","route":"/pathways/cancer-immunity-cycle/"},{"id":"tumor-microenvironment","kind":"pathway","name":"Tumour microenvironment (TME)","route":"/pathways/tumor-microenvironment/"}],"institution":[{"id":"humanitas","kind":"institution","name":"IRCCS Humanitas Research Hospital","route":"/institutions/humanitas/"},{"id":"sitc","kind":"institution","name":"Society for Immunotherapy of Cancer","route":"/institutions/sitc/"},{"id":"uchicago-cancer","kind":"institution","name":"University of Chicago Medicine Comprehensive Cancer Center","route":"/institutions/uchicago-cancer/"}]}}