The fact that the immune system itself attacks tumor cells, called immunotherapy, has revolutionized oncology treatments in recent years. However, only between 20 and 40% of patients respond positively to these therapies. Predicting in which people the treatment is most likely to be successful is the focus of much current research. A group of scientists from the Institute for Biomedical Research (IRB) in Barcelona, led by Núria López-Bigas and Abel González Pérez, has located five factors that determine the response of patients to immune checkpoint inhibitors (CPIs), a type of immunotherapy widely used in oncology treatments.
The results, published in the journal Natural genetics After an exhaustive analysis of data from 479 patients with metastatic tumors, they represent a “significant advance” because in addition to allowing a more precise identification of patients for whom the treatment may work, they make it possible to treat people who are not currently considered candidates for immunotherapy – as is the case for liver or kidney carcinomas – could benefit from it, explains the IRB.
Until now, available studies have focused on observing specific characteristics of tumors or patients’ immune systems. The results of this new research assume what the researchers called “independent factors.” “Individual biomarkers have been identified, but our results suggest that many of these biomarkers may be different versions of the same underlying factors,” says Dr. González-Pérez.
The more mutations, the more possibilities for attack.
What are these factors? On the one hand, the “tumor mutational load.” If it mutates a lot, it generates more neoantigens, which allows the immune system to recognize and attack them more easily. On the other hand, the presence of cytotoxic T lymphocytes is essential for immunotherapy to be effective. “Greater infiltration of these cells is directly linked to a better response to treatment,” the study confirms.
The researchers also found a relationship with “transforming growth factor beta (TGF-β) activity in the tumor microenvironment” because high activity “can suppress the immune response.” In addition, two key factors are the treatment previously received by the patient – those who have been treated before tend to respond less well – and the tumor proliferation index. If it is high, which occurs in more aggressive cancers, the chances of survival after treatment are lower, concludes the research, which validated these variables in six independent cohorts with a total of 1,491 patients with lung, colon and melanoma cancer. The data analyzed come from a public database of the Dutch Hartwig Medical Foundation.
Dr. López-Bigas considers the results “an important step in understanding how different tumor and patient characteristics contribute to response,” and the team hopes that the five factors will be used to “guide treatment decisions in the future.” “This advance could have important clinical implications, as it could prevent patients with a low probability of response from suffering the side effects of CPIs, which can lead to autoimmune diseases, and, in addition, help reduce the cost of treatment,” he said. the IRB in a statement.
The study provides valuable information to improve personalized medicine, but it has limitations. The researchers acknowledge that “the accuracy of these models for possible future clinical application should be validated by prospective clinical trials.” However, it is a challenge to be able to access data as complete and comprehensive as that used in research on a larger volume of patients, which would be essential to “generate more accurate models,” they say.
