Research carried out in the Department of Medicine at the University of Fribourg on therapies which target blood vessels supplying blood to a tumour has killed two birds with one stone. The researchers have not only been able to demonstrate that these therapies have an effect on the immune system in that they encourage the T-lymphocytes to attack the tumour, but they have also identified a new therapeutic target against the formation of metastases.

Targeted treatments which are alternative or complementary to radiotherapy and chemotherapy are being used more and more in the care of cancer patients, including those with breast  cancer. Of these, the antiangiogenic treatments, designed to inhibit the formation of blood vessels supplying blood to the tumour, affect the immune system whose complex mechanisms are still not well understood.

Domino effect
The researchers of the Department of Medicine at the University of Fribourg employed an experimental model of cancer of the breast in order to study the effects of inhibiting the VEGF receptor – a protein whose role is to trigger the formation of new blood vessels – on various immune system cells. Their results show that this inhibition blocks the activity of cells induced by the tumour which are capable by themselves of inhibiting the T-lymphocytes. Once “liberated”, the latter increase their activity, thus curbing the growth of the breast cancer.

Blocking metastases
The spread of tumorous cells and the formation of metastases in other organs are the main cause of cancer relapse. This study has also enabled the identification of a molecule (arginase 1) which is strongly expressed in white blood cells in the presence of a cancer and which promotes the formation of metastases. The inhibition of this molecule stimulates the activation of the anti-tumorous T-lymphocytes and greatly reduces the formation of metastases.

These results have potential implications for breast cancer patients. On the one hand, antiangiogenic treatments could be used in combination with existing immunotherapy treatments. On the other, arginase inhibitors are already at a clinical development stage and could be tested for the prevention of relapses.

C. Secondini, O. Coquoz, L. Spagnuolo, L. Ciarloni, T. Spinetti, S. Peyvandi, F. Botta, C. Bourquin and C. Rüegg. Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade. Oncoimmunology, 2017 in press