{"entity":{"id":"idea-bio1-spatial-clone-immune-map","kind":"idea","name":"Map which tumour clones sit next to which immune cells before choosing therapy","aka":[],"tldr":"New imaging shows where every cell type sits in a tumour slice. Using it to see which sub-populations are hidden from immune cells could explain why immunotherapy fails in parts of a tumour.","summary":"Spatial transcriptomics and multiplex imaging can now assign genotype-inferred clones and immune phenotypes to positions in a section. The proposal is a diagnostic-biopsy pipeline reporting clone-immune neighbourhoods: which subclones are immune-excluded, which express MHC, and whether resistant clones cluster in immune deserts. This would be used to decide whether to combine a targeted agent with immunotherapy or a stroma-modifying agent.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["single-cell-spatial","digital-pathology-ai"],"targets":[],"drugs":[],"companies":["10x-genomics"],"institutions":[],"pathways":[],"terms":["cold-vs-hot","tils"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-immunotherapy-response"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Tumours in which the dominant resistant subclone occupies an immune-excluded niche progress on immunotherapy combinations at a higher rate than tumours with immune-infiltrated resistant subclones, and this is measurable at baseline.","rationale":"Heterogeneity is spatial as well as genetic; immune exclusion is a local property. Current bulk PD-L1 or TMB scores erase both dimensions.","test":"Retrospective spatial profiling of 200 pre-treatment biopsies from immunotherapy trials with known outcomes; prospective validation if the neighbourhood score adds to PD-L1 and TMB.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-bio1-spatial-clone-immune-map/","neighbours":{"technology":[{"id":"digital-pathology-ai","kind":"technology","name":"Digital pathology & AI","route":"/technologies/digital-pathology-ai/"},{"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/"}],"term":[{"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/"}],"bottleneck":[{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}]}}