# Reprogramme suppressive macrophages instead of trying to delete them

Source: https://onco.cc/ideas/idea-bio2-trem2-myeloid-reprogramming/  
OnCo record `idea-bio2-trem2-myeloid-reprogramming` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Tumours fill with immune cells that protect them. Earlier drugs tried to remove those cells and failed. Newer ones aim to switch them to the attacking side.

## Summary

CSF1R inhibitors depleted macrophages broadly and produced little benefit outside tenosynovial giant cell tumour, plausibly because depletion removes useful cells alongside harmful ones. TREM2, MARCO and LILRB2 mark specific suppressive macrophage states in human tumour single-cell atlases, and antibodies against them are in early trials. The proposition is state-switching, verified by on-treatment biopsies, rather than depletion.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Blockade of a suppressive macrophage state marker shifts the intratumoural myeloid transcriptional programme towards antigen presentation and raises response to checkpoint blockade in tumours pre-selected for high suppressive macrophage content.
- Rationale: Human single-cell data consistently identify TREM2-high macrophage states in poorly responding tumours, and genetic ablation in mice restores checkpoint response. Selecting patients by myeloid content, rather than treating everyone, is the step the CSF1R programmes skipped.
- Proposed test: A biopsy-mandated phase 2 in myeloid-high tumours with paired pre- and on-treatment single-cell profiling; kill the programme if the myeloid state does not shift, regardless of response rate.
- Maturity: early-clinical
- Actor: industry

## 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/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/)
- people: [Caetano Reis e Sousa](https://onco.cc/people/caetano-reis-e-sousa/)
- 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/)

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