# Clear the suppressive neutrophils out of pancreatic tumours first

Source: https://onco.cc/ideas/idea-bio2-cxcr2-neutrophil-blockade/  
OnCo record `idea-bio2-cxcr2-neutrophil-blockade` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Pancreatic tumours are packed with a type of white blood cell that shuts down the immune attack. Blocking the signal that recruits them may open the tumour to immunotherapy.

## Summary

CXCR2-dependent recruitment of granulocytic myeloid-derived suppressor cells is a dominant immunosuppressive mechanism in pancreatic and some head and neck cancers, and CXCR2 inhibition plus checkpoint blockade improved survival in genetically engineered mouse models. Human trials of CXCR1/2 inhibitors with chemotherapy or checkpoint blockade have been small and biomarker-light. The decisive step is patient selection by neutrophil infiltration measured on tissue, not by blood counts alone.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: In tumours pre-selected for high granulocytic myeloid infiltration on baseline biopsy, CXCR2 blockade plus checkpoint therapy reduces intratumoural neutrophil density by half and produces objective responses in a population where checkpoint therapy alone gives almost none.
- Rationale: The mechanism is one of the best supported in autochthonous pancreatic models, and the intervention is a small molecule with an established safety profile from inflammatory disease programmes.
- Proposed test: Biopsy-selected phase 2 with paired tissue myeloid quantification as primary endpoint and response as secondary; abandon if neutrophil density does not fall despite adequate exposure.
- 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: [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Digital pathology & AI](https://onco.cc/technologies/digital-pathology-ai/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- terms: [Desmoplasia (tumour stroma)](https://onco.cc/terms/desmoplasia/), [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/)

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