# Map which tumour clones sit next to which immune cells before choosing therapy

Source: https://onco.cc/ideas/idea-bio1-spatial-clone-immune-map/  
OnCo record `idea-bio1-spatial-clone-immune-map` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012): https://doi.org/10.1056/NEJMoa1113205

## Connected records

- technologies: [Digital pathology & AI](https://onco.cc/technologies/digital-pathology-ai/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- companies: [10x Genomics](https://onco.cc/companies/10x-genomics/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Tumour-infiltrating lymphocytes (TILs)](https://onco.cc/terms/tils/)
- bottlenecks: [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)

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