ideasIdea
Clear the suppressive neutrophils out of pancreatic tumours first
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.
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.
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.
What would test it
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
Who has to act
industry
Cost to try
Medium ($1M to $50M)
Years to first evidence
6
Bottlenecks it attacks
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.
- No one can predict who responds to immunotherapy · Checkpoint drugs cure some patients and do nothing for most. We still cannot tell the two apart before treating.