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Immunotherapy treatment could be improved by blocking molecules that help tumour blood vessels grow, according to two new lab-based studies.
Tumours grow new blood vessels to supply cancer cells with oxygen and nutrients. But certain features of these vessels mean that they can block the entry of cancer-fighting immune T-cells.
In these two new research papers, published back to back in Science Translational Medicine, scientists found that stopping these blood vessels from forming in mice boosted the effects of a type of immunotherapy, allowing cancer-attacking T cells to enter the tumour.
T-cells are part of the immune system that immunotherapy treatment aims to boost to fight cancer. But tumours can use various tricks to evade the treatment’s effects, such as growing abnormal blood vessels which don’t allow immune cells to reach their target. According to study author Professor Michele De Palma from École Polytechnique Federale de Lausanna (EPFL) in Switzerland, this latest research serves as a reminder that such tricks are often just round the corner.
Scientists from EPFL and Katholieke Universiteit Leuven in Belgium blocked different molecules that are required for the formation of tumour blood vessels, a process known as angiogenesis.
Looking at mice with different types of cancer, including breast and pancreatic, the researchers found that blocking blood vessel growth caused immune cells to flood the tumour. But the tumour cells then responded by producing more of a stop signal, or checkpoint, on their surface called PD-L1. When this sticks to a molecule called PD-1, found on cancer-fighting T cells, it prevents them from attacking.
Both of these molecules are targets of immunotherapies known as checkpoint blockers.
The combination of the checkpoint blockers and the blood vessel blockers shrank tumours and improved survival in some of the mice.
Professor Aymen Al-Shamkhani, a Cancer Research UK expert on immunotherapy from the University of Southampton, said: “These are interesting studies that have the potential to improve responses in patients treated with PD-1 checkpoint blockers.
“These drugs only work in some cancer types, such as melanoma, lung and bladder cancer, and in those cancers typically only 20-40% of patients respond to the treatment. Interestingly, non-responsive tumours are often lacking T-cells.
“Therefore, combining PD-1 checkpoint blocking with other targeted therapies is highly attractive, particularly if this increases the number of tumour-attacking T-cells that enter the tumour.”
According to Dr Adel Samson, a Cancer Research UK expert on immunotherapy from the University of Leeds, the findings suggest that drugs targeting tumour blood vessel formation should be tested in combination with immunotherapies in clinical trials.
“The future success of cancer therapies lies in the evidence-based design of combination therapies that target cancers in multiple different ways; a goal that will only be achieved through rigorous preclinical studies and well-designed clinical trials,” he added.
Schmittnaegel, M. et al. (2017). Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade. Science Translational Medicine. 9.
Allen, E. et al. (2017). Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through HEV formation. Science Translational Medicine. 9.