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Experts have demonstrated that an innovative, non-invasive imaging technique can be harnessed to monitor oncolytic virotherapy, a rapidly advancing field of cancer treatment.
In a recent study, the researchers successfully used immuno-positron emission tomography (immuno-PET) to track the immune response of mice with head and neck squamous cell carcinoma (HNSCC). After administering a specialised virus to the tumour, the team was able to examine the changes that occurred in the entire body.
This approach could offer a clearer picture of the body-wide effects that localised treatment can have, which could play a critical part in guiding clinical decision-making and optimising therapeutic strategies.
The study was led by researchers at The Institute of Cancer Research, London, and the findings were published in the Journal of Nuclear Medicine. Cancer Research UK, the Oracle Cancer Trust and the Chellaram Foundation all provided funding, as did The Institute of Cancer Research (ICR), which is both a research institute and a charity.
A virus engineered for its mission
Oncolytic virotherapy sounds somewhat counterintuitive because viruses are typically associated with unpleasant symptoms. However, the idea is relatively straightforward. Scientists engineer viruses so that they infect and kill cancer cells while sparing healthy ones. As the virus destroys the tumour from within, it can also alert the immune system, effectively turning the cancer into its own vaccine.
In this study, the researchers used RP1, an experimental oncolytic virus based on the herpes simplex virus. RP1 can be injected directly into tumours and is designed to not only kill cancer cells but also stimulate an immune response that may extend beyond the injection site.
They chose to test it in HNSCC, which can be difficult to treat and often has an inconsistent response to immunotherapy. Not all patients benefit from immune checkpoint drugs, which aim to unleash the immune system by blocking molecular ‘brakes’ such as PD‑1 and its partner protein PD‑L1.
The reason for this is hard to determine because immune responses within tumours can be patchy and hard to measure. Another challenge has been understanding whether a local treatment such as oncolytic virotherapy is really activating the immune system system‑wide or only having an effect in the injected tumour.
Imaging the immune response, not just the tumour
Instead of relying on tissue biopsies, which are invasive and limited to a few locations, the researchers turned to a technique called immuno‑PET. PET is already widely used to track tumours, but immuno‑PET goes a step further by using radioactive tracers that bind to selected proteins present on immune or cancer cells.
In this case, the tracer was designed to bind to PD‑L1, a key immune checkpoint protein that helps tumours shield themselves from attack. By tracking PD‑L1 across the body, the team could see where and when immune responses were changing.
The researchers carried out their study in mouse models for head and neck cancer. After injecting RP1 into a tumour, they scanned the animals a few days later using immuno‑PET and compared the results with those of untreated controls.
The scans revealed something striking. Three days after the viral injection, PD‑L1 levels rose sharply – not in the treated tumours themselves, but in the spleen and the lymph nodes that drain the tumour area. These are key hubs of immune activity. By day seven, PD‑L1 levels in these organs had returned to baseline.
This pattern suggests that the local viral treatment triggered a strong but temporary systemic immune response.
Why this matters for patients
Although the work was done in mice, its implications reach well beyond the laboratory. Immunotherapies are often combined in the clinic, but oncologists currently have limited tools to see how these combinations affect the immune system as a whole.
PD‑L1 levels are usually measured using biopsies from a single tumour site. However, immune responses can differ dramatically between tumours and organs, and they can change over time. Immuno‑PET offers a non‑invasive way to monitor these dynamics repeatedly across the entire body.
The ability to capture the immune system’s response as it unfolds, without repeatedly sampling tissues, could be extremely valuable for optimising how and when immunotherapies are given.
Indeed, the research suggests that understanding timing may be particularly important. The transient spike in PD‑L1 seen in immune organs indicates that there may be a narrow window during which combining oncolytic viruses with checkpoint drugs would be most effective.
“A powerful tool to evaluate treatment response”
The authors are careful to stress that immuno‑PET is not yet a routine clinical tool for this purpose. However, several PD‑L1 imaging agents are already moving through early clinical trials, raising the possibility that similar approaches could one day help guide treatment decisions in people.
First author Julia Höbart, a former PhD student in the Division of Radiotherapy and Imaging at the ICR, said:
“This work demonstrates how immuno-PET can effectively provide whole-body insights into immune dynamics. It enables the assessment of both local changes within the tumour and systemic immune responses across other organs, which is not possible using any other diagnostic method.”
Lead author Dr Gabriela Kramer-Marek, Group Leader of the Preclinical Molecular Imaging Group at the ICR, said:
“Immuno-PET is currently undergoing a new, transformative phase, driven by the rapid expansion of immuno-oncology. This includes not only checkpoint inhibitors but also a growing range of novel therapies designed to activate or modulate the tumour immune microenvironment, such as radiopharmaceuticals and, more recently, oncolytic viruses.
“There is increasing recognition that, for certain cancers, therapies can be delivered locally rather than systemically, allowing for direct administration into the tumour and thereby reducing systemic toxicity. In this context, immuno-PET emerges as a powerful tool to evaluate treatment response.”
For now, the study provides a rare glimpse of the immune system reacting in real time to cancer therapy. By making the invisible visible, it adds an important piece to the puzzle of why some immunotherapy combinations succeed while others fall short. The next step will be to find ways of ensuring that patients receive only the effective treatments.
Image credit: Kiril Ukr from Pixabay (modified)