2024-09-12 11:18:50
Immunotherapy has revolutionized cancer treatment by using the immune system to attack tumor cells. However, only 20% to 40% of patients respond well to this treatment, and the effectiveness varies depending on the type of cancer. Determining which patients will benefit from immunotherapy is one of the main areas of research.
Until now, studies have focused on the specific characteristics of tumors, their environment or the patient’s immune system, which has generated uncertainty about which antibodies are really effective.
A group of Biomedical Research Institute (IRB) of Barcelona has identified five independent factors that determine patients’ response to checkpoint inhibitors (CPI), a common immunotherapy in cancer treatment. The results, published in ‘Nature of Genetics‘, provides a framework for current and future oncologists, and opens the door to better personalization of oncological treatments, making it possible to more accurately predict which patients will respond positively to immunotherapy.
The study suggests that patients with liver or kidney cancer, who are not currently candidates for immunotherapy, may benefit from it. The group led by Núria López-Bigas and Abel González-Pérez, in collaboration with international institutions, analyzed the genomic and clinical data of 479 patients with metastatic tumors treated with CPIs, collected from the Hartwig Medical Foundation database.
Five key factors for immunotherapy
Researchers identified five independent factors that influence response to immunotherapy and patient survival:
The burden of change means (TMB): Tumors with more mutations produce neoantigens that facilitate recognition and attack by the immune system.
Infiltration of cytotoxic T cells: Great infiltration of these cells increases the effectiveness of immunotherapy.
TGF-β activity in the tumor microenvironment: High activity of this factor suppresses the immune response, negatively affecting survival.
Pretreatment: Patients with prior treatments tend to respond worse to immunotherapy.
Tumor proliferative potential: More aggressive tumors are associated with worse response to treatment.
Towards a more personalized oncology
These five factors provide a solid foundation for organizing current knowledge on immunotherapy biomarkers. The study suggests that many individual predictors may be components of these underlying factors, allowing for a more accurate response prediction. Furthermore, a multivariate model that combines these factors has been shown to be more effective than current biomarkers, such as variable burden, in predicting which patients will respond well.
The study validated these five factors in six independent groups, which included 1,491 patients with different types of cancer, such as lung, colon and melanoma, emphasizing their clinical value. The researchers hope to have more data to improve the accuracy of the models, which will need to be validated in prospective clinical trials.
This advance represents a key step in understanding how tumor and patient characteristics influence the immune response. According to López-Bigas, the goal is for these factors to be integrated into clinical practice, making therapeutic decisions in the future.
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