In a groundbreaking study, Australian researchers at Wesley Research Institute have uncovered a crucial factor that determines whether patients with head and neck cancer will respond to immunotherapy – a finding that could pave the way for more effective treatments and improved survival rates.
Head and neck cancer is an aggressive disease often diagnosed at advanced stages. Each year, nearly one million new cases are reported worldwide. Frequently linked to HPV, particularly in younger patients, it has a high mortality rate, killing up to 50% of those affected.
Beyond its high mortality rate, head and neck cancer significantly impacts patients’ quality of life, often affecting their ability to eat, speak and swallow.
Immune checkpoint inhibitors (ICIs), a class of drugs that help restore the immune system’s ability to detect and destroy cancer cells, have shown promise in extending survival for some patients. These therapies, including PD-1/PD-L1 inhibitors, work by activating immune cells to attack tumours. However, many patients remain unresponsive to ICIs, highlighting an urgent need for better treatment strategies.
The new study, conducted by researchers from Wesley Research Institute’s Queensland Spatial Biology Centre (QSBC), The University of Queensland’s Frazer Institute, Princess Alexandra Hospital and the Royal Brisbane and Women’s Hospital, has revealed that the presence of dense layers of macrophages – immune cells that typically engulf and destroy harmful invaders – may actually create a barrier that prevents immune cells from attacking the tumour. This immune blockade appears to be a key factor in why some patients fail to respond to ICI therapy.
Using the QSBC’s advanced imaging techniques, the research team closely examined immune interactions in tumour samples from 35 patients with head and neck cancer.
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Naei, V.Y., Tubelleza, R., Monkman, J. et al. Spatial interaction mapping of PD-1/PD-L1 in head and neck cancer reveals the role of macrophage-tumour barriers associated with immunotherapy response. J Transl Med 23, 177 (2025). https://doi.org/10.1186/s12967-025-06186-y
They discovered that in patients who did not respond well to immunotherapy, certain immune cells called macrophages formed dense layers around the tumour, acting as a barrier that blocked the body’s natural immune defences. In contrast, patients who responded positively to treatment had clusters of B and T cells – key immune defenders – gathering at the tumour’s edge, helping to mount a stronger attack against the cancer.
This discovery fundamentally shifts how we understand and visualise tumour-immune interactions
QSBC Scientific Director and lead researcher Associate Professor Arutha Kulasinghe
“For years, we’ve focused on PD-L1 expression alone as a predictor of immunotherapy response. But our study highlights the importance of mapping and visualising the tumour and immune interactions at the tumour site. If we can target these macrophage barriers, we may be able to improve treatment outcomes for many more patients.”
A crucial component of this breakthrough was the use of innovative imaging technology developed by Navinci, a Swedish protein interaction company. Navinci’s specialised assay enabled researchers to visualise and analyse immune cell interactions at the tumour site with unprecedented precision and resolution. By applying this technology to clinical samples in Australia, the team was able to generate critical insights into why certain patients respond to treatment while others do not.
The study’s findings suggest that future immunotherapy approaches could involve strategies to break down these immune barriers, either through new drug combinations or techniques that enhance immune cell penetration into the tumour. Additionally, the implications of this research extend beyond head and neck cancer, with potential applications for lung, bladder, colorectal and melanoma.
Associate Professor Brett Hughes, a co-author of the study from the Royal Brisbane and Women’s Hospital, emphasised the clinical significance of the findings.
Immunotherapy has revolutionised cancer treatment, but we’ve seen that only a fraction of patients benefit. By identifying these immune interactions, we now have new tools to understand where therapies may be effective, which could lead to better personalised therapies and improved survival rates for our patients
Associate Professor Brett Hughes
With further research, the findings could help refine patient selection for immunotherapy, ensuring that those most likely to respond receive treatment while others are offered alternative therapeutic strategies.
The study represents a major step forward in the fight against head and neck cancer, with broader implications for immunotherapy in other cancers as well.
The research, supported by the Passe and Williams Foundation and the Princess Alexandra Research Foundation, has been published in The Journal of Translational Medicine, offering new hope for patients and oncologists worldwide.