{"entity":{"id":"idea-bio2-liver-niche-kupffer-reprogramming","kind":"idea","name":"Reprogramme the liver's own immune cells to refuse metastases","aka":[],"tldr":"The liver is where bowel cancer most often spreads. Drugs delivered straight into the liver's blood supply could retrain its resident immune cells to reject arriving cancer cells.","summary":"Kupffer cells and liver sinusoidal endothelium determine whether arriving colorectal cells die or seed, and hepatic arterial infusion is an established delivery route with dedicated pumps and an experienced clinical community. Combining regional delivery with a myeloid agonist (CD40 agonist, TLR9 agonist or STING agonist) targets the niche rather than the tumour, at doses that would be intolerable systemically.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["sting-agonist","radioembolisation-tare"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oligometastatic"],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-tme-immunosuppression"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regional hepatic delivery of a myeloid-agonist regimen after resection of colorectal liver metastases reduces the new-hepatic-lesion rate at 18 months compared with systemic therapy alone.","rationale":"Regional floxuridine infusion already improves liver-specific outcomes, proving the route matters. CD40 agonism converts liver macrophages to an anti-tumour state in murine colorectal liver metastasis models, and systemic CD40 agonists are limited mainly by hepatotoxicity and cytokine release.","test":"Dose-finding regional infusion study with paired liver biopsies for myeloid phenotype, then a randomised trial with new-hepatic-lesion-free survival as primary endpoint.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},"route":"/ideas/idea-bio2-liver-niche-kupffer-reprogramming/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"radioembolisation-tare","kind":"technology","name":"Radioembolisation (TARE / SIRT, yttrium-90)","route":"/technologies/radioembolisation-tare/"},{"id":"sting-agonist","kind":"technology","name":"STING & innate immune agonists","route":"/technologies/sting-agonist/"}],"term":[{"id":"oligometastatic","kind":"term","name":"Oligometastatic disease","route":"/terms/oligometastatic/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-metastasis-biology","kind":"bottleneck","name":"Metastasis is understood least and studied last","route":"/bottlenecks/b-metastasis-biology/"}],"paper":[{"id":"paper-dillekas-cancer-med","kind":"paper","name":"Are 90% of deaths from cancer caused by metastases?","route":"/key-papers/paper-dillekas-cancer-med/"}]}}