Study of the University of Coimbra aims to overcome unsuccessful immunotherapy in bladder cancer

^{Abridged version in English by Diana Taborda}

A research team of the Faculty of Medicine of the University of Coimbra (FMUC) is studying possible immunoevasion mechanisms that limit the success of immunotherapy in bladder cancer, leading the way for the development of new drugs to combat this type of tumour, which, in advanced stages, has a high mortality rate.

Through various mechanisms, bladder cancer (which is more common in men), "manages to evade and inhibit the action of our body's immune system, allowing it to grow without being destroyed by the action of our immune cells (immune evasion). Our project focuses on one of these mechanisms that escapes the immune system, which is linked to the metabolism of adenosine, and which we think is one of the ways in which bladder cancer limits the action of our natural protection mechanisms, also reducing the effectiveness of immunotherapy drugs already used today," explains the researcher and urologist Frederico Furriel.

These drugs (PD-1 and PD-L1 inhibitors), he adds, "are only 20-30% effective, and this is certainly because there are other ways through which the tumour proceeds to immunoevasion, namely through adenosine".

The results already obtained, based on analyses of clinical samples from patients, show that the growth of bladder cancer is followed by "a profound change in the microenvironment, towards a greater immunosuppression, which is evidently favourable to the tumour. On the other hand, we were able to identify a greater expression of adenosine in the tumour microenvironment, when compared to the normal tissue", says Frederico Furriel, pointing out that the most important discovery so far, "was to find out that there is a connection between these facts: the greater the concentration of adenosine, the greater the immunosuppression, which is in accordance with our hypothesis".

These studies, which are taking place at the Institute for Clinical and Biomedical Research (iCBR) at FMUC, consist of inducing the "formation of bladder cancer in an animal model (mice), and then administering drugs capable of suppressing the adenosine circuit, in order to assess whether this leads to a reduction in the size of the tumour or other improvement features. We will also associate these drugs with those that are already used today in immunotherapy, to determine if this combined therapy leads to better results than isolated therapy."

This study may "lead the way for the development and use (after rigorous clinical trials) of specific drugs, either in monotherapy or associated to others that already exist, leading ultimately to the improvement of prognosis of patients with bladder cancer. All advances are welcome for the treatment of a disease with a high mortality rate", further highlights Frederico Furriel.

"If our results are successful, we may, at a later stage, move on to clinical trials in humans to test new immunotherapy drugs, possibly in association with those already used today", he concludes.