Summary
A bioRxiv preprint reports that an early interferon-responsive neutrophil program tracked resistance to anti-PD-1 therapy in preclinical models of triple-negative breast cancer. Genetic disruption of interferon signalling in neutrophils improved treatment responses in those models.
A bioRxiv preprint reports that an early interferon-responsive program in neutrophils was associated with resistance to anti-PD-1 immunotherapy in preclinical models of triple-negative breast cancer. The researchers also found that genetically disrupting interferon signalling in neutrophils improved treatment efficacy and promoted durable anti-tumour immune memory in these models.
The study combined longitudinal single-cell and spatial transcriptomics with neutrophil-specific genetic perturbations. Its findings point to an immune-cell signal that may help explain why responses to checkpoint blockade differ, while remaining at the preclinical research stage.
An early neutrophil signal tracked treatment response
Neutrophils are immune cells involved in the body's rapid responses to infection and tissue damage. Interferons are signalling proteins that help coordinate immune activity; interferon-stimulated genes (ISGs) are genes whose activity increases in response to these signals.
The researchers identified an ISG program in neutrophils that appeared before tumours showed an overt difference in growth. In the models studied, successful anti-PD-1 treatment was accompanied by an early decline in interferon-responsive neutrophils in both blood and tumour tissue. When interferon signalling in these cells persisted, treatment resistance was more likely.
The timing matters because it raises the possibility that changes in immune cells could offer an early indication of how treatment is going, rather than simply reflecting later differences in tumour size. The authors propose dynamic neutrophil interferon activity as a candidate blood-based biomarker; the reported findings do not amount to a clinically established test.
Spatial analyses also found that regions enriched for tertiary lymphoid structures—organised groupings of immune cells within tissue—were inversely associated with interferon-responsive neutrophils during effective treatment. This spatial relationship adds context to the immune changes seen alongside response.
Genetic perturbations support a role in resistance
To test whether neutrophil interferon signalling could affect treatment response, the researchers genetically disrupted signalling through either type I or type II interferons in neutrophils. Both interventions enhanced anti-PD-1 efficacy and promoted durable anti-tumour immune memory in the preclinical models.
These perturbation results strengthen the case that neutrophil interferon activity is more than a marker accompanying resistance in those models: altering the pathway changed treatment outcomes. The findings therefore identify a possible therapeutic direction as well as a candidate way to monitor early immune dynamics.
The work concerns preclinical triple-negative breast cancer models, not a clinical trial in patients. It was posted as a bioRxiv preprint on October 1, 2026, and its proposed biomarker and therapeutic implications require evaluation in further research, including in people receiving immunotherapy.