High‑grade gliomas are the most common and aggressive tumours of the central nervous system, with a devastating prognosis of 12–15 months of median survival after diagnosis. The high infiltrative capacity of tumour cells, together with their location in an “immune‑privileged” organ protected by the blood–brain barrier, is one of the main causes of treatment failure. Immunotherapy with immune‑checkpoint inhibitors has recently emerged as one of the most promising therapeutic strategies for extending survival in selected groups of patients. However, clinical outcomes in glioblastoma have been largely disappointing due to its low immunogenicity, the immune‑privileged nature of the central nervous system and the strongly immunosuppressive tumour microenvironment. For these reasons, it is essential to characterise the tumour‑adjacent region known as infiltrated peripheral oedema (IPE), where key immune processes take place, and to identify its underlying molecular profile. This knowledge would enable more aggressive and effective surgical interventions, while also allowing the selection of patients who may benefit from combined immunotherapy approaches targeting specific molecular pathways.
The classical delineation of tumour regions has been useful for identifying areas associated with glioblastoma prognosis, but its implementation in clinical practice presents important limitations. Our recent findings in the infiltrated peripheral oedema (IPE) region show that: (1) patient survival can be predicted through its vascularity, and (2) this region often evolves into active tumour tissue only months after surgery. These insights increase the uncertainty surrounding how far to resect during surgical planning, leading some hospitals to replace standard surgical protocols with supratotal resections, including extreme cases in which the entire lobe containing the tumour is removed.
In this project, we propose the use of non‑invasive nosological imaging techniques that enable surgeons to accurately visualise the cellular and molecular characterisation of peritumoral regions (IPE: infiltrated peripheral oedema), including vascularity/angiogenesis, cell proliferation and immune suppression.
To this end, we first propose a project to develop and validate a procedure and system for planning surgery in high‑grade glial tumours (PRODUCT 1). This system will be based on nosological imaging enriched with spatial information linked to cancer identity hallmarks, such as angiogenesis, cell proliferation and immunosuppression.
To support the decision of whether or not to resect this area of infiltrated peripheral oedema (IPE), it is necessary to define the medical‑imaging characteristics that reflect its underlying cellular and molecular processes. This will be achieved through panels of mutations and gene‑expression profiling in the infiltrated peripheral oedema region, and by correlating these findings with imaging biomarkers in the same area.
This panel will enable the development of a precision immunosuppressive‑characterisation surgical kit (PRODUCT 2). During surgery, it will allow the performance of digital PCR to support intraoperative decision‑making regarding tumour resection or the placement of immunotherapy treatment in the region of infiltrated peripheral oedema.
