Costa Rican microbiologist Javier Mora Rodríguez is part of an international team that studies the power of a molecule to combat breast cancer.
The molecule is called interleucine-38 (IL-38)and has the ability to regulate the immune system. Together with scientists from Spain and Germany, he has studied for years how this compound could be used to help fight the disease.
The hope of these scientists is to achieve an immunotherapy. Immunotherapies seek to strengthen the cells of the immune system so that they attack and destroy cancer cells, but without harming healthy cells in the process. These treatments are used alone or in combination with other therapies.
In their studies, the researchers saw that, by inactivating this molecule and “neutralizing” it, the immune system can be stimulated and a specific type of defense cells awakened, this would improve the immune response against the tumor and increase the effectiveness of chemotherapy.
The results of these investigations were published in the journal Journal for ImmunoTherapy of Cancer.
So far, it has only been proven in laboratory cells and mice. However, these steps in basic science are necessary before being tested in humans.
“A significant group of patients do not react to current immunotherapy. “We decided to explore additional pathways that could influence the antitumor immune response and improve the future efficacy of existing treatments,” Mora specified in interview with the University of Costa Rica (UCR).
They focused on one subtype of breast cancer. There are several types of breast cancer that are not treated equally because their characteristics are different. The researchers focused on metastatic breast cancer (where cancer cells have spread to other parts of the body) and triple negative. Triple negative cancer tends to grow and spread faster, resulting in fewer treatment options as well as a worse prognosis.
“This type of cancer does not respond well to immunotherapies. Therefore, it is necessary to look for new strategies to reactivate that immune response that attacks the tumor,” explained the specialist.
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What is the molecule against breast cancer?
Previous research that Mora conducted determined that interleukin-38 (IL-38) helped maintain balance in the body, because it prevents inflammatory responses from getting out of control.
However, in cancer it works differently and its normal action rather it could act in favor of cancer.
As? In this scenario, IL-38 “turns off the alarms” of the immune system and allows tumors to “grow undisturbed.”
With this in mind, scientists wanted to see if inactivating IL-38 would free up the body’s defenses and give them the opportunity to attack cancer more effectively.
The team worked with genetically modified mice to develop tumors similar to those seen in humans.
They concluded that blocking IL-38 slowed the growth of tumors in mice.
But that was not all, the inactivation brought allies. γδ (gamma-delta) T cells, known for their ability to recognize cancer cells, began to grow around the tumor.
These cells, which are not normally seen in many cancers, seemed to take a leading role in the battle. Furthermore, its presence attracted another group of important cells of the immune system: conventional dendritic cells (cDC1). These latter cells are essential for activating CD8+T cells: “the most lethal soldiers” of the immune system.
“We saw that (CD8+T) were capable of attacking cancer cells and reducing the size of tumors,” Mora said.
The new molecule would “remove the disguise” of cancer cells so that the defense system can recognize it. Tumors are capable of “disguising themselves”, this makes them resistant to current chemotherapy and immunotherapy.
However, by neutralizing IL-38, it was as if the cancer dropped its disguise: the immune system can clearly see the adversary and attack it directly.
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An allied molecule of chemotherapy
Once with these results, the team decided to go one step further. He combined the molecule with chemotherapy and applied it to another group of mice with the same type of cancer.
Andreas Weigert, a German researcher who works with Mora, told the UCR that chemotherapy induces the death of tumor cells. In turn, dying tumor cells release more IL-38. Therefore, they thought that blocking IL-38 would improve results.
These showed that neutralizing the molecule not only activated the immune system, but also made the tumor more vulnerable to chemotherapy.
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Future in the fight against breast cancer
These results are not applicable to humans and would not necessarily work in patients with triple-negative or metastatic breast cancer. Therefore, clinical trials in people are necessary to see if, in the future, patients will have new options.
For now, scientists are confident that this is a door for tumors that have almost no therapeutic options.
And this would not only be an option for breast tumors. There are others, such as glioblastoma multiforme, a malignant brain tumor that does not work efficiently with immunotherapy. Blocking IL-38 could give hope to these patients, although more studies are needed.
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