i3S study validates strategy for developing vaccines against colorectal cancer

A team of i3S researchers has identified persistent immunological vulnerabilities in colorectal tumours that could be exploited in the development of personalised therapeutic cancer vaccines.

The study, now published in the prestigious scientific journal Gut, focused on colorectal tumours known to produce large numbers of neoantigens—altered molecules that can be recognised by the immune system as danger signals. In most cases, the immune system can detect these signals and eliminate the tumour cells.

The problem arises when this mechanism fails. "In these cases, the tumour creates an immunosuppressive environment that prevents the immune system from completing its task, allowing the tumour to develop," explains Helena Xavier Ferreira, the study's first author.

Although the tumour continues to grow, it does not escape immune recognition. In fact, many of its cells acquire mutations that lead to the production of additional neoantigens. "The challenge is to help the immune system, which has been suppressed by the tumour's immunosuppressive environment, do what it already knows how to do: attack cells displaying these neoantigens," adds Carlos Resende, one of the study's senior authors.

This discovery has important clinical implications. By identifying the neoantigens that elicit a genuine immune response, the study provides essential knowledge for the development of therapeutic cancer vaccines. These vaccines are designed according to the specific genetic characteristics of each patient's tumour.

"We are looking at one of the most advanced expressions of personalised medicine. Each vaccine must be tailored to an individual patient, taking into account the mutations and neoantigens present in their tumour. The same vaccine will not be effective in different patients," says José Carlos Machado, who leads the research group.

In addition to supporting the development of new therapeutic strategies, the study also improves our understanding of how tumours evolve under immune system pressure. The findings strengthen the prospect of a new generation of personalised immunotherapies capable of exploiting the unique vulnerabilities of each tumour while enhancing the body's natural ability to fight cancer.