# Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours

Source: https://onco.cc/ideas/idea-moon-cold-to-hot-programme/  
OnCo record `idea-moon-cold-to-hot-programme` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

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

## Sources

- 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): https://doi.org/10.1001/jamanetworkopen.2019.2535

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Oncolytic viruses](https://onco.cc/technologies/oncolytic-virus/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/), [STING & innate immune agonists](https://onco.cc/technologies/sting-agonist/)
- targets: [CD47](https://onco.cc/targets/cd47/), [FAP](https://onco.cc/targets/fap/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)
- key papers: [Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs](https://onco.cc/key-papers/paper-haslam-jama-netw-open/), [Expression and Clinical Significance of CD47 in Colorectal Cancer: A Review](https://onco.cc/key-papers/paper-cd47-colorectal-cancers-basel-2025/), [Overcoming immunotherapeutic resistance in PDAC: SIRPα-CD47 blockade](https://onco.cc/key-papers/paper-cd47-pancreatic-pharmacol-res-2022/), [Phase II Clinical Trial and Preclinical Evaluation of a Novel CD47 Blockade Combination in Refractory Microsatellite-Stable Metastatic Colorectal Cancer](https://onco.cc/key-papers/paper-cd47-colorectal-cancer-res-commun-2025/)

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