Researchers from Uppsala and Magdeburg awarded ERC Synergy Grant to advance cancer immunotherapy

Over the last ten years, the successful implementation of immunotherapy represents a true paradigm shift in cancer treatment. We know today that tumour-reactive T cells – a type of immune cell – inside tumours can be made more potent through a treatment called immune checkpoint blockade. Here special medications are used to release the ‘brakes’ in the immune system that prevent T cells from attacking the tumour, which can significantly improve patients’ chances of survival. It is also known now that if T cells are absent in tumours, checkpoint blockade tends not to work. Since T cells are recruited into tumours from the circulation, the tumour vasculature plays an important role in forming the immune landscapes in tumours.

In the project VASC-IMMUNE, now funded by the ERC, the researchers will target and customize blood vessels in tumours to increase T cell infiltration and maintain their function.

“We will utilize the fact that in melanoma, some patients respond to immunotherapy, while others do not. We know that responders tend to have higher T cell infiltration and that immune hubs can form in such cancer tissues. By connecting the vascular landscape to the immune landscape in tumour material from responding and non-responding patients, we hope to identify factors in the vascular-immune crosstalk that govern this,” explains Thomas Tüting.

The researchers will also study glioblastoma, a malignant brain cancer that represents a formidable challenge, and where immunotherapy has not yet delivered.

“I have been studying glioblastoma vessels and their interaction with immune cells for many years. I’m confident that by comparing the vascular and immune landscapes of melanoma and glioblastoma we will identify genes whose activity determines how tumour vessels interact with immune cells. Once we have learnt this, we need to specifically transfer important gene regulatory factors to optimize tumour vessel function to improve T cell recruitment and support formation of immune hubs,” says Anna Dimberg.

However, to target and reprogramme tumour vessels in cancer patients possess a significant challenge. Magnus Essand’s research groups will develop a novel virus that can specifically target tumour vessels while sparing normal blood vessels.

“We have already shown that this is possible in mouse models of glioblastoma and together we will now translate this finding to human tumour vessels, not only in glioblastoma and melanoma but tumour vessels in general. This is why the project has such great transformational potential,” says Magnus Essand.

The VASC-IMMUNE project is for six years and will start in February 2025. The researchers expect to work closely and share data, expertise and personnel to advance the project and at the same time create a rich and stimulating environment for young researchers to grow.