{"entity":{"id":"idea-bio2-spatial-signature-cdx","kind":"idea","name":"Turn the map of immune cells inside a tumour into a standardised test","aka":[],"tldr":"Whether immune cells are next to cancer cells matters more than how many there are. Turning that spatial picture into a reliable, standardised test would predict response better.","summary":"Spatial features such as the distance from cytotoxic T cells to tumour cells, the presence of immune-excluded phenotypes and B-cell aggregates outperform PD-L1 and tumour mutational burden in retrospective series. No spatial assay has been standardised as a companion diagnostic, and platform variability, staining variability and analytical drift are unaddressed. Reference tissue standards and a locked analysis pipeline are the prerequisites.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["single-cell-spatial","digital-pathology-ai","companion-diagnostic","pathology-foundation-model"],"targets":[],"drugs":[],"companies":["10x-genomics","paige","bostongene","lunit"],"institutions":[],"pathways":[],"terms":["tps","cps","tils","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation","b-ai-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A locked spatial signature with defined reference materials predicts checkpoint benefit with a higher c-statistic than PD-L1 immunohistochemistry across at least three tumour types, and is reproducible between laboratories to within a defined tolerance.","rationale":"PD-L1 scoring itself became clinically usable only after harmonisation efforts and defined scoring rules, despite its known weakness. Spatial biology has better biological content and is following the same path, but has not yet done the metrology.","test":"A multi-laboratory ring study on shared reference slides to quantify reproducibility, then retrospective validation of a locked signature in banked trial tissue with pre-registered thresholds.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":5},"route":"/ideas/idea-bio2-spatial-signature-cdx/","neighbours":{"technology":[{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/"},{"id":"digital-pathology-ai","kind":"technology","name":"Digital pathology & AI","route":"/technologies/digital-pathology-ai/"},{"id":"pathology-foundation-model","kind":"technology","name":"Pathology & radiology foundation models","route":"/technologies/pathology-foundation-model/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"}],"company":[{"id":"10x-genomics","kind":"company","name":"10x Genomics","route":"/companies/10x-genomics/"},{"id":"bostongene","kind":"company","name":"BostonGene","route":"/companies/bostongene/"},{"id":"lunit","kind":"company","name":"Lunit","route":"/companies/lunit/"},{"id":"paige","kind":"company","name":"Paige AI","route":"/companies/paige/"}],"term":[{"id":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"tps","kind":"term","name":"Tumour proportion score (TPS)","route":"/terms/tps/"},{"id":"tils","kind":"term","name":"Tumour-infiltrating lymphocytes (TILs)","route":"/terms/tils/"}],"bottleneck":[{"id":"b-ai-validation","kind":"bottleneck","name":"AI that is built but not validated or deployed","route":"/bottlenecks/b-ai-validation/"},{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"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/"}]}}