{"entity":{"id":"idea-moon-cold-to-hot-programme","kind":"idea","name":"Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours","aka":[],"tldr":"Immunotherapy works in tumours that immune cells can enter and ignores those that shut them out. Systematically test ways to open up the shut-out tumours, measured with spatial maps.","summary":"Most pancreatic, prostate, colorectal (microsatellite-stable), ovarian and glioma tumours are immune-excluded or immune-desert. Candidate strategies include stromal modulation (FAP, TGF-beta, CXCR4 antagonists), innate agonists (STING, TLR), oncolytic viruses, radiotherapy priming, and myeloid reprogramming (CD47, CSF1R). Each has been tested piecemeal. The proposal is a coordinated programme with standardised spatial immune profiling before and after each intervention in window-of-opportunity trials, a shared classification of exclusion mechanisms, and adaptive combination trials that match the mechanism of exclusion to the reprogramming strategy.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["pancreatic","colorectal","prostate","ovarian"],"sections":[],"technologies":["single-cell-spatial","sting-agonist","oncolytic-virus","checkpoint-inhibitor"],"targets":["fap","cd47"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open","paper-cd47-pancreatic-pharmacol-res-2022","paper-cd47-colorectal-cancers-basel-2025","paper-cd47-colorectal-cancer-res-commun-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mechanism-matched reprogramming converts at least a third of treated cold tumours to inflamed phenotypes on spatial profiling and produces objective responses to checkpoint inhibition in indications where they are currently rare.","rationale":"Exclusion has multiple distinct mechanisms; unselected combinations have failed because the mechanism was not matched. Spatial profiling now makes matching feasible.","test":"Window-of-opportunity platform in pancreatic and microsatellite-stable colorectal cancer with paired biopsies; primary endpoint conversion rate on spatial immune score, secondary response to subsequent checkpoint inhibitor.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":8},"route":"/ideas/idea-moon-cold-to-hot-programme/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"},{"id":"sting-agonist","kind":"technology","name":"STING & innate immune agonists","route":"/technologies/sting-agonist/"}],"target":[{"id":"cd47","kind":"target","name":"CD47","route":"/targets/cd47/"},{"id":"fap","kind":"target","name":"FAP","route":"/targets/fap/"}],"term":[{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"}],"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/"}],"paper":[{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","route":"/key-papers/paper-haslam-jama-netw-open/"},{"id":"paper-cd47-colorectal-cancers-basel-2025","kind":"paper","name":"Expression and Clinical Significance of CD47 in Colorectal Cancer: A Review","route":"/key-papers/paper-cd47-colorectal-cancers-basel-2025/"},{"id":"paper-cd47-pancreatic-pharmacol-res-2022","kind":"paper","name":"Overcoming immunotherapeutic resistance in PDAC: SIRPα-CD47 blockade","route":"/key-papers/paper-cd47-pancreatic-pharmacol-res-2022/"},{"id":"paper-cd47-colorectal-cancer-res-commun-2025","kind":"paper","name":"Phase II Clinical Trial and Preclinical Evaluation of a Novel CD47 Blockade Combination in Refractory Microsatellite-Stable Metastatic Colorectal Cancer","route":"/key-papers/paper-cd47-colorectal-cancer-res-commun-2025/"}]}}