By eliminating regulatory T cells—a type of white blood cell that inhibits the immune response and protects cancer—researchers have enabled treatment-resistant tumors to respond to immunotherapy in experimental and preclinical models.

The discovery, the result of an international scientific collaboration between researchers from the United Kingdom and the Centro Ciencia & Vida (FCV-USS), opens the possibility of exploring new therapeutic pathways and highlights the value of supporting long-term science.

Behind the finding, published in the specialized journal Immunity, is an international scientific network connecting three Chilean researchers, two of whom work at some of the leading European academic institutions: University College London and the University of Oxford.

A team of Chilean scientists has developed an experimental strategy capable of reversing glioblastoma resistance to immunotherapy. The breakthrough, which opens a new therapeutic path for one of the most aggressive brain tumors with the poorest prognosis, was recently published in Immunity , one of the most influential scientific journals in the field of immunology.

The key to the finding lies in a mechanism that suppresses the action of regulatory T cells—white blood cells that inhibit the immune response and protect cancer—thereby allowing other immune system cells, cytotoxic T cells, to regain their ability to attack tumor cells.

In preclinical models, this strategy enabled tumors that were previously refractory to treatment to respond favorably to antibody-based therapies.

The discovery demonstrates that by eliminating certain immunosuppressive elements present in the tumor microenvironment, it is possible to reprogram the immune response to be effective against glioblastoma, explained Dr. Felipe Gálvez-Cancino, a Chilean researcher based in the United Kingdom who currently leads a laboratory at the Centre for Immuno-Oncology at the University of Oxford and is one of the study's lead authors.

“Glioblastoma is not only one of the deadliest forms of cancer, but we still lack truly effective therapies for the benefit of people suffering from this condition. The goal is to activate the immune system so that it fights it from within, becoming an ally in the struggle against this pathology.”

The work was co-led by Dr. Sergio Quezada, from the University College London Cancer Institute, with the collaboration of Dr. Alvaro Lladser, director of the Centro Basal Ciencia & Vida and professor at the Universidad San Sebastián in Chile.

The study reveals that once regulatory T cells are eliminated, the tumor responds favorably to immune checkpoint inhibitors and antibody-based treatments. This type of immunotherapy consists of blocking the signals that enable tumor growth, thereby reactivating the immune system to directly attack malignant cells, opening a promising path for the design of new oncological therapies.

Globally, glioblastoma affects between 3 and 5 people per 100.000 inhabitants per year, with an average survival rate not exceeding 15 months from diagnosis. In Chile, although there are no specific statistics, a similar incidence is estimated. Given this scenario, the scientific community is betting on new biotechnological alternatives such as immunotherapy.

Chilean science against cancer

The World Health Organization (WHO) recognizes immunotherapy as a promising tool in cancer treatment, especially those based on immune checkpoints. The United Nations agency considers these new developments as a form of targeted treatment that has the potential to achieve greater effectiveness with fewer side effects compared to conventional chemotherapy.

In recent years, in fact, the agency has proposed the incorporation of 6 checkpoint-related inhibitors into the complementary list of essential medicines.

Dr. Alvaro Lladser, director of the Centro Basal Ciencia & Vida at the Fundación Ciencia & Vida of the USS, valued the research project as proof of the relevance of having scientists in Chile who are globally connected and can lead high-impact studies for global problems such as cancer.

“This collaboration stems from the interaction generated in the advanced courses and international symposia we have organized at the Center. These instances foster the exchange of knowledge and the formation of collaboration networks between students and researchers from Chile and the best research centers in the world.”

Dr. Lladser recalled that one of the study's lead researchers, Dr. Gálvez-Cancino, was trained at the Centro Ciencia & Vida and then moved into a high-level international scientific environment. “This model has proven to be tremendously successful, and Felipe is an example of this. The fact that he is now leading research with global impact is a source of pride and also a clear sign that investing in science and advanced training yields concrete results.”

From his laboratory at the University College London Cancer Institute, Dr. Sergio Quezada highlighted the long-term collaboration established with the institution founded by, among others, the National Science Prize winner, Dr. Pablo Valenzuela; and more recently with the USS and, in particular, with Dr. Lladser's laboratory, which has materialized in the permanent exchange of knowledge and technology, as well as various publications.

“Beyond the discoveries and publications, there is a relationship of trust and also contact with young Chilean researchers that I like very much, which has allowed us to achieve exchanges and training for Chilean students in my laboratory in London, while we have sent young researchers to the foundation to participate in different courses, generating more exchange and collaborations.”

Reactivating the immune system

The elimination of regulatory T cells—the primary axis of the strategy described in Immunity—promotes the “recruitment” of macrophages, a type of white blood cell that plays a key role by acting as “sentinel cells” that detect, engulf, and destroy abnormal cells, in addition to releasing chemical signals to trigger a massive response in the body.

For Chilean scientists, this understanding opens a promising line of research to manipulate the tumor microenvironment and develop oncological therapies that improve patient prognosis. Dr. Gálvez-Cancino noted that his group is already collaborating with a biotechnology company in Canada that is developing molecules targeting the therapeutic target of regulatory T cell suppression and conducting studies focused on glioblastoma.

The Oxford researcher specifies that, although the antibody in question had already been described previously, what was not known was whether it worked in this specific pathological context or what happened when regulatory T cells were eliminated. According to Dr. Gálvez-Cancino, the approval of drugs against this particular cancer in the last 10 years is practically zero (the last alternative barely improved survival by 6 months), a reality that could evolve thanks to immunotherapies.

“Metastatic melanoma, for example, which 20 years ago was practically a death sentence, can now be treated with immunotherapy, and many people manage to survive because their own immune system attacks the tumor. In the case of glioblastoma, we believe—and I truly believe it—that it is also possible to achieve something similar. That is the big difference compared to what already exists: immunotherapies, which are already changing the course of other tumors, aim for the immune system to do the work of attacking the cancer.”

One of the forgotten cancers

Glioblastoma develops from glial cells, which support the central nervous system. Fast-growing and invasive, it often infiltrates regions of the brain that cannot be removed without causing severe damage. Currently, it represents about 50% of all gliomas (tumors that originate in the glial cells of the brain or spinal cord), and its diagnosis is usually confirmed by magnetic resonance imaging and biopsy.

The most common treatment combines surgery, radiotherapy, and chemotherapy, but its high resistance to available therapies makes recurrence almost inevitable.

From Oxford, Dr. Felipe Gálvez-Cancino warns that a quarter of the cancers diagnosed in the world are rare or very low-incidence tumors, such as glioblastoma. And yet, most of them receive marginal attention from the point of view of research and biomedical development. “Working on them is not only a scientific challenge but also an obligation to thousands of diagnosed patients.”

“The experience with the coronavirus vaccine in Oxford showed that it is possible to shorten the times between basic research and clinical application. This influences the design of trials for more agile oncological therapies, especially in the development of vaccines,” concluded the Chilean scientist, whose next research aims to contribute to the design of strategies against extremely rare and aggressive childhood tumors.

By: Luis Francisco Sandoval. S&M Comunicaciones Agency.