Immunotherapies are treatments that aim to stimulate the immune system to fight cancer. The strategy has proven quite effective against some tumors – including melanoma or lung cancer – but inefficient against many others. A team headed by ICREA researcher Eduard Batlle and funded by the BBVA Foundation has discovered why and proven that it can also be used against colon cancer.
The use of immunotherapy drugs started five years ago. These treatments help patients’ immune systems to attack cancer cells by deactivating the shield they develop for protection. However, most colon tumors remained undetectable for the immune system until the team led by Eduard Batlle managed to identify and deactivate the cause for this blindness.
The paper – just published in British scientific journal Nature – shows that the TGF-beta hormone is responsible for the immune system's inability to recognize colon tumors. By inhibiting the activity of TGF-beta, the cells of the immune system infiltrate and recognize the tumor, fight the cancer, and even stop colon tumors from metastasizing to the liver and lung.
The researchers have demonstrated that, in combination with available immunotherapies, the TGF-inhibitor would allow the immune system to efficiently eliminate already established metastases, which would otherwise kill the individual in a question of weeks.
To carry out this study, the IRB Barcelona research team used a preclinical mouse model that mimics the human disease. Scientist Daniele Tauriello, postdoctoral fellow and first author of the article, induced four of the most common mutations present in advanced human colon tumors in mice. This model allowed the researchers to examine how cancer cells evade the immune system.
Beyond colon cancer
In the same issue of Nature there is another study, by North American pharmaceutical company Genentechthat, on the lack of response of bladder cancer patients to immunotherapy, which draws the same conclusions as Batlle’s team.
“This second study demonstrates that the discovery goes beyond colon cancer. It appears that many types of tumor use the same strategy—increasing the expression of TGF-beta in the environment—to evade the immune system. Patients with these tumors may also benefit from immunotherapies based on the inhibition of this hormone,” say the scientists at IRB Barcelona.
The study also involved the Department of Oncology and Pathology at the Hospital del Mar de Barcelona.
The study also received funding from the Olga Torres Foundation, the Josef Steiner Foundation, the European Research Council, the Ministry of Economy and Competitiveness through ERDFs, the Botín Foundation, and Global Santander Universities Division. Eduard Batlle is also a member of the CIBERONC network (Biomedical Research Networking Centre in Oncology), from which he also receives funds for his lab.