A new study published today in Nature Cancer, led by Bruno Silva-Santos, group leader at GIMM Foundation, and Sofia Mensurado, demonstrates for the first time the effectiveness of an immunotherapy developed by the team of researchers in a model of colorectal cancer. The immunotherapy is based on the use of a type of white blood cell, which exists in the body in low quantities and has the ability to identify and kill cancer cells. This cell therapy, called DOT cells, comes from expanding and stimulating these white blood cells to make them more powerful at eliminating tumours.

In 2021, Bruno Silva-Santos saw his discovery of DOT cells applied to patients with acute myeloid leukemia for the first time in a clinical trial in the United States. However, in the case of colorectal cancer, the most common cancer in Portugal and the second leading cause of cancer death in the country, the vast majority of patients do not respond well to the available immunotherapies. Now, the research team has proven in trials with tumor cells from patients and in mice that DOT cells have the potential to treat this type of cancer. “In this article, we explore two crucial points: proving that DOT cells have the potential for colorectal cancer treatment and identifying how we could enhance their antitumor effect,” says Rafael Blanco-Domínguez, the first author of the study. “We had very promising results. We discovered that DOT cells are effective against colorectal cancer and that their anti-tumor action can be enhanced by administering a supplement to the mice,” adds Sofia Mensurado, co-leader of the study. This supplement is butyrate, a molecule that is naturally produced by the bacteria in our intestines and which increases the ability of DOT cells to recognize cancer cells. “Additionally, blocking molecular brakes (“immune checkpoints”)—a well-established immunotherapeutic strategy used successfully in some types of cancer—was tested in combination with DOT cells and increased the effectiveness of the therapy against colorectal cancer,” explains Rafael Blanco-Domínguez.

“DOT cells are particularly interesting as a therapy because they do not react to genetic differences between individuals. This characteristic makes it possible to produce DOT cells from healthy donors and create a ‘cell bank’ ready to use, to treat different patients, with the ambition of creating a ‘universal’ cellular immunotherapy,” shares Bruno Silva-Santos, co-leader of the study, adding that he has dedicated his career to studying the immune system because “its interaction with tumor cells is fascinating while also being quite challenging in its clinical application.”

The results obtained now in mice are very promising and pave the way for the possibility of applying this immunotherapy in the treatment of colorectal cancer. On the other hand, it also leaves open the possibility of developing more efficient immunotherapies for other solid tumors.

(*) Blanco-Domínguez R, Barros L, Carreira M, van der Ploeg M, Condeço C, Marsères G, Ferreira C, Costa C, Ferreira CM, Déchanet-Merville J, de Miranda NFC, Mensurado S*, Silva-Santos B*. (2025) Dual modulation of cytotoxic and checkpoint receptors tunes the efficacy of adoptive Delta One T cell therapy against colorectal cancer. Nature Cancer. doi.org/10.1038/s43018-025-00948-9