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ICREA reserach professor Eduard Batlle and first author of the study Daniele Tauriello in the Colorectal Cancer Laboratory (M. Minocri, IRB Barcelona).
 14.02.2018

IRB Barcelona paves the way to the use of immunotherapy to treat aggressive colon tumours and their metastasis

A team headed by ICREA researcher Eduard Batlle, from the Institute for Research in Biomedicine (IRB Barcelona) at the Barcelona Science Park, discovers that immune system-stimulating treatments combined with a TGF-beta inhibitor are effective against colon cancer. In a study published today in the journal Nature, scientifics explain that the hormone TGF-beta is responsible for the “blindness” of the immune system to colon cancer cells. The work paves the way for the development of the first treatment based on immunotherapy for patients with metastatic colon cancer and for those patients with poor prognosis but who have not yet developed metastasis.

 

In a short space of time, immunotherapy, that is to say therapies based on stimulating the immune system against cancer cells, has become a powerful approach to treat cancers such as melanoma and lung cancer. However, to date, most colon tumours appeared to be unresponsive to this kind of therapy. Given this observation, it was hypothesized that this kind of tumour was simply invisible to the immune system. 

“The few clinical immunotherapy trials done in patients with the most common subtype of colon cancer were not giving good results and we didn’t understand why this was happening,” explains Eduard Batlle.

By inhibiting the activity of TGF-beta, the cells of the immune system infiltrate and recognise the tumour, fight the cancer, and even stop colon tumours from metastasizing to the liver and lung in a preclinical mouse model that mimics the human disease. In addition, and more importantly, the researchers have demonstrated that the combination of a TGF-beta inhibitor with available immunotherapies boost the anti-tumour effect, allowing the immune system to efficiently eliminate already established metastases, which would otherwise kill the individual in a question of weeks.
 

Model that mimics aggressive human colon cancer

The scientist Daniele Tauriello, postdoctoral fellow and first author of the article, induced four of the most common mutations present in advanced human colon tumours in mice. “The development of the animal model took us four years but we hit the nail on the head,” he says.

After confirming the similarity of the mouse tumours with those in humans, they built a biobank of tumour organoids—3D mini-tumours— to then graft them in a controlled manner in immunocompetent mice. “For studies of the immune system, the tumour has to be of mouse origin otherwise the animal would reject it,”he explains. This animal model, which mimics the main features of metastatic colon cancer in patients, allowed the researchers to examine how cancer cells evade the immune system.
 

Beyond colon cancer

Around 40 to 50% of colon cancer patients relapse in the form of metastasis, with the tumours reproducing mainly in the liver and lung. “When a diagnosed of advanced stage colon cancer is given, oncologists do not have access to efficient treatments to cure the patient,” explains Eduard Batlle.

This study paves the way for the development of the first treatment based on immunotherapy for patients with metastatic colon cancer and for those patients with poor prognosis but who have not yet developed metastasis.

“Oncologists and pharmaceutical companies will soon start clinical assays that combine TGF-beta inhibitors, which are already in clinical use, with immunotherapies. We are convinced that many colon cancer patients will benefit from this therapeutic strategy,” they say.
 

►Reference article:

Daniele VF Tauriello, Sergio Palomo-Ponce, Diana Stork, Antonio Berenguer-Llergo, Jordi Badia-Ramentol, Mar Iglesias, Marta Sevillano, Sales Ibiza, Adria Cañellas, Xavier Hernando-Momblona, Daniel Byrom, Joan A Matarin, Alexandre Calon, Elisa I Rivas, Angel R Nebreda, Antoni Riera , Camille Stephan-Otto Attolini and Eduard Batlle. “TGF-beta drives immune evasion in genetically reconstituted colon cancer metastasis” Nature (2018). DOI: http://dx.doi.org/10.1038/nature25492
 

►For further information: IRB Barcelona website [+]