In the study, led by Bruno Silva-Santos, lead researcher at the GIMM Foundation - Gulbenkian Institute of Molecular Medicine, and researcher Sofia Mensurado and published today in the scientific journal Nature Cancer, the team proved that this new cell therapy, called DOT cells, which comes from the expansion and stimulation of these white blood cells to make them more powerful in eliminating tumors, is effective in the case of colorectal cancer, the second most deadly cancer in Portugal.

These white blood cells can identify and kill cancer cells, but they are in low numbers in the body.

“In this article, we explored two crucial points: proving that DOT cells have potential for the treatment of colorectal cancer and identifying how we could enhance their antitumor effect,” explains Rafael Blanco-Domínguez, first author of the study.

In the case of colorectal cancer, most patients do not respond well to available immunotherapies.

In this work, the team was able to prove in tests with tumor cells from patients and in mice that DOT cells have the potential to treat this type of cancer.

“We discovered that DOT cells are effective against colorectal cancer and that their antitumor action can be enhanced by giving a supplement to mice,” adds Sofia Mensurado.

The supplement in question is butyrate, a molecule that is naturally produced by bacteria in the intestine and that increases the ability of DOT cells to recognize cancer cells.

Additionally, blocking molecular barriers (“immune checkpoints”) - an immunotherapeutic strategy already successfully established in some types of cancer - was tested in combination with DOT cells and increased the efficacy of cancer therapy.

In 2021, researcher 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 of America.

“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 for use to treat different patients, with the ambition of creating a ‘universal’ cellular immunotherapy,” explains Bruno Silva-Santos.

The researcher adds that he has dedicated his career to studying the immune system because “its interaction with tumor cells is fascinating and at the same time quite challenging in its clinical application.”

The results now obtained pave the way for the possibility of applying this immunotherapy in the treatment of colorectal cancer and, on the other hand, also provide proof that it may be possible to develop more efficient immunotherapies for other solid cancers.

The research was developed at the GIMM Foundation – Gulbenkian Institute of Molecular Medicine, in collaboration with the Leiden University Medical Center, Netherlands; with the University of Bordeaux, France; with the Santa Maria Hospital and the Faculty of Medicine of the University of Lisbon.