Chemotherapy may trigger immune response that protects ovarian tumours

Researchers at The Wistar Institute have identified a mechanism that may explain why ovarian tumours can become resistant to chemotherapy. The study [1], published in The Journal for ImmunoTherapy of Cancer, shows that chemotherapy can activate an inflammatory pathway that recruits immune cells which ultimately help protect cancer cells from treatment.

Chemotherapy resistance remains one of the greatest challenges in ovarian cancer, with many patients initially responding to treatment before developing recurrent disease that is harder to treat. The new findings suggest that resistance is not driven solely by changes within cancer cells themselves, but also by interactions between tumours and their surrounding microenvironment.

The researchers found that chemotherapy increased levels of interleukin-1 beta (IL-1β), an inflammatory signalling molecule that can activate immune responses. Elevated IL-1β was particularly associated with tumours that responded poorly to chemotherapy.

Further investigation revealed that IL-1β encourages the recruitment of neutrophils, a type of immune cell, into the tumour environment. Rather than supporting anti-cancer activity, these neutrophils appeared to protect tumours by suppressing cancer-fighting T cells and releasing neutrophil extracellular traps (NETs), structures that reduced the effectiveness of chemotherapy drugs.

Using preclinical models, the team showed that blocking IL-1β signalling or preventing NET formation could restore tumour sensitivity to chemotherapy. Patient tumour samples also showed increased neutrophil activity and NET formation following chemotherapy, supporting the findings from laboratory studies.

“Our findings suggest chemotherapy resistance is also an immunology problem,” said Dr Nan Zhang, senior author of the study. “The treatment meant to kill the tumour can trigger inflammatory responses that help it survive.”

The discovery could open new possibilities for improving chemotherapy outcomes, as IL-1β-targeting therapies are already available and approved for other medical conditions. The researchers are now investigating whether combining these approaches with existing cancer treatments, including immune checkpoint inhibitors, could help overcome resistance.

While further research is needed to understand the full complexity of the tumour microenvironment, the study highlights the importance of targeting not only cancer cells but also the immune signals that influence tumour behaviour.

More information online

1.    Chemotherapy Induces an IL1β-dependent Neutrophil Recruitment and Activation that Promote Chemoresistance in Metastatic Ovarian Cancer published in The Journal for ImmunoTherapy of Cancer, 2026. Online publication.