An international study with participation from researchers at the BDSLab-ITACA of the Universitat Politècnica de València (UPV) has discovered that the architecture of blood vessels inside and around a brain tumour is associated with treatment efficacy. This opens up new possibilities for treating brain tumours by targeting their blood vessels along with pharmacological treatment. The study’s results have been published in the journal Neuro-Oncology.

The research originated from a phase 2 trial that assessed the efficacy of pembrolizumab, a type of immunotherapy based on immune checkpoint inhibitors, specifically for treating brain metastases of various histologies. «We explored the relationship between the efficacy of this immunotherapy treatment and vascular architecture in the hopes of identifying possible mechanisms of intracranial response or resistance to immunotherapy in metastases,» explains Elies Fuster, a researcher from the Biomedical Data Science Lab (BDSLab) at the ITACA Institute of the Universitat Politècnica de València.

44 patients

The study used vascular architecture images (VAI), a histologically validated quantitative metric, to evaluate tumour vascular physiology in vivo. The VAI was utilized to analyze tumour and peritumoral vascular architecture before and after treatment with pembrolizumab in 44 trial participants.

«We found that brain tumours that responded well to treatment had a more balanced vasculature of small and large vessels and showed better blood flow. This allows us to suggest that a balanced network of blood vessels can help the treatment work better,» states Elies Fuster.

Thus, this study has identified a potential biomarker (vascular architecture images, VAI) for predicting the response to this type of immunotherapy in brain metastases. Moreover, it provides a foundation for future studies that explore vascular architecture modulators and their effects on immune activity within the tumour microenvironment, which could lead to more specific and effective treatment strategies.

«By identifying the structural characteristics of the vasculature that correlate with positive responses to this type of immunotherapy, new therapeutic targets could be developed to improve the efficacy of immunotherapy. Future studies could focus on combining pembrolizumab with agents that promote a more balanced vascular network or reverse the negative effects of hypoxia on immune surveillance. Such combined treatments could significantly improve outcomes for patients with brain metastases, offering a more personalized and effective approach to cancer therapy,» highlights Elies Fuster.

A Revolution for the Treatment of Brain Metastases and Other Types of Cancer

The following steps in this line of research will focus on the relationship between the architecture of tumour blood vessels and the immune system’s ability to fight cancer.
«By combining advanced omics analyses with detailed studies of these blood vessels’ function, we want to uncover the precise mechanisms by which the structure of tumour blood vessels can enhance or hinder the efficacy of immunotherapies. This comprehensive approach aims not only to confirm the results obtained so far but also to pave the way for developing new, more effective combined treatments that target both the tumour and its vascular support system, revolutionizing the approach to the treatment of brain metastases and other types of cancer,» concludes Elies Fuster.

This study, involving the UPV, was led by the Massachusetts General Hospital Cancer Center (Harvard Medical School), the Athinoula A. Martinos Center for Biomedical Imaging (Massachusetts General Hospital), and the Department of Physics and Computational Radiology (Oslo University Hospital).

Additionally, researchers from reference institutions such as Dana-Farber Cancer Institute (Harvard Medical School), Massachusetts Institute of Technology, University of Pennsylvania School of Medicine, and Yale School of Medicine also participated.

Source: UPV’s Communication Area