Immuno-PET Imaging Reveals Body-Wide Immune Response to Oncolytic Virotherapy in Head and Neck Cancer
Key Insights
Researchers at The Institute of Cancer Research, London (search), used immuno-PET to track PD-L1 (search) dynamics across the entire body after oncolytic virus injection in mouse models of head and neck cancer.
Scans revealed a sharp but transient spike in PD-L1 (search) levels in the spleen and tumor-draining lymph nodes three days after treatment, returning to baseline by day seven.
The findings suggest a narrow therapeutic window during which combining oncolytic viruses with checkpoint inhibitors may be most effective.
A new imaging study has demonstrated that immuno-positron emission tomography (immuno-PET) can capture the immune system's body-wide response to oncolytic virotherapy in real time, offering a potential tool to guide clinical decision-making and optimize combination immunotherapy strategies.
The research, led by scientists at The Institute of Cancer Research (ICR), London, and published in the Journal of Nuclear Medicine, tracked immune dynamics in mouse models of head and neck squamous cell carcinoma (search) (HNSCC) following injection of an experimental oncolytic virus.
Making the invisible visible
Oncolytic virotherapy involves engineering viruses to selectively infect and kill cancer cells while sparing healthy tissue. As the virus destroys the tumor 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, which is designed to be injected directly into tumors and stimulate an immune response that may extend beyond the injection site.
HNSCC was chosen as the test model because it can be difficult to treat and often has an inconsistent response to immunotherapy. Not all patients benefit from immune checkpoint drugs targeting PD-1 and PD-L1 (search), and the reasons are hard to determine because immune responses within tumors can be patchy and difficult to measure.
Instead of relying on invasive tissue biopsies limited to a few locations, the team turned to immuno-PET, which uses radioactive tracers that bind to selected proteins on immune or cancer cells. In this case, the tracer was designed to bind to PD-L1 (search), a key immune checkpoint protein that helps tumors shield themselves from attack.
A transient systemic immune response
The scans revealed a striking pattern. Three days after RP1 was injected into a tumor, PD-L1 (search) levels rose sharply — not in the treated tumors themselves, but in the spleen and the lymph nodes draining the tumor 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. The transient spike in PD-L1 (search) observed in immune organs indicates that there may be a narrow window during which combining oncolytic viruses with checkpoint drugs would be most effective.
Clinical implications beyond the laboratory
Although the work was conducted 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 (search) levels are usually measured using biopsies from a single tumor site, yet immune responses can differ dramatically between tumors and organs and can change over time.
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, added: "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."
Dr. Kramer-Marek further noted: "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."
Parallel clinical progress with VCN-01 and durvalumab
In a separate but related development, a multidisciplinary team from the Catalan Institute of Oncology (search) (ICO), the Bellvitge Biomedical Research Institute (IDIBELL (search)), and Vall d'Hebron University Hospital, in collaboration with Theriva Biologics, published Phase I clinical trial results in Clinical Cancer Research exploring a different oncolytic virus combined with immunotherapy in advanced head and neck cancer.
The trial investigated VCN-01, a genetically modified virus that replicates exclusively inside tumor cells, combined with the PD-L1 (search) inhibitor durvalumab in 20 patients with recurrent or metastatic squamous cell carcinoma of the head and neck. VCN-01 was developed by Theriva Biologics from technology created in the laboratory of Dr. Ramon Alemany of the Cancer Immunotherapy group at ICO and IDIBELL (search).
Results showed that the combination was viable and safe under certain conditions. Promising signs of antitumor activity were detected, with some patients exceeding 17 months of survival and more than 60% of participants alive after one year of follow-up.
According to Ricard Mesía, head of the Medical Oncology Service at ICO Badalona and author of the study: "This treatment is not only viable, but also manages to profoundly modify the tumour microenvironment. Analysis of the biopsies shows a significant increase in active immune cells within the tumor." Mesía stressed that "this change is especially relevant because it could make immunotherapy-resistant tumours sensitive to drugs such as durvalumab again."
Notably, some patients who had stopped responding to immunotherapy showed a new response to subsequent treatments after receiving the combination of VCN-01 and durvalumab, pointing to a possible reactivation of tumor sensitivity.
A path toward more personalized treatment
The researchers stress that these results will need confirmation in larger, controlled clinical trials. However, the use of oncolytic viruses to modify the tumor microenvironment could open a new therapeutic avenue for patients with advanced head and neck cancer, an area with significant unmet need for innovation in oncology.
Several PD-L1 (search) imaging agents are already moving through early clinical trials, raising the possibility that immuno-PET approaches could one day help guide treatment decisions in patients. By making the immune system's response visible in real time, the imaging study adds an important piece to the puzzle of why some immunotherapy combinations succeed while others fall short.