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Dr. Abel González-Pérez and Dra. Núria López-Bigas. Photo / IRB Barcelona.
 13.09.2024

Five key factors predict the response of cancer patients to immunotherapy

A team of researchers at IRB Barcelona, based in the Barcelona Science park, has identified five independent factors that predict cancer patients’ response to checkpoint inhibitors (CPIs). The study,  published in Nature Genetics, validates these factors in more than 1,400 patients and diverse types of cancer. These findings provide a framework to interpret biomarkers of response to CPIs and suggest a future pathway to improve personalised cancer medicine.

Immunotherapy has transformed cancer treatment in recent years by enabling the immune system to attack tumour cells. However, only 20-40% of patients respond positively to immunotherapy, and these rates vary across different types of cancer. Predicting which patients will respond to immunotherapy and which will not is currently a highly active area of research. Numerous studies conducted so far have focused on the specific characteristics of tumours, their microenvironment, or the patient’s immune system. As a result, which of the proposed biomarkers represent the same underlying factors or how many independent factors influence the effectiveness of this therapy remains unclear.

Researchers at IRB Barcelona have identified five key, independent factors that determine patients’ response and survival after receiving checkpoint inhibitors (CPIs), a type of immunotherapy widely used in cancer treatment. These findings, published in Nature Genetics, provide a reference framework for current and future biomarkers of immunotherapy response. They could also, in the future, entail a pathway to a significant advancement in the personalisation of cancer treatments, helping to more accurately identify those patients who are likely to benefit from immunotherapy. The results suggest that patients with certain types of tumours, who are currently not considered candidates for immunotherapy (such as those with liver or kidney carcinomas) might benefit from this type of treatment.

The team led by Dr. Núria López-Bigas and Dr. Abel González-Perez, from the Biomedical Genomics laboratory at IRB Barcelona, in collaboration with researchers from several international centres, has addressed this issue through a comprehensive analysis of genomic, transcriptomic, and clinical data from 479 patients with metastatic tumours, who received CPI treatment. These data are from a public database generated by  the Dutch Hartwig Medical Foundation.

“We used an unbiased approach to analyse thousands of molecular and clinical features and identified five independent factors that influence response to immunotherapy and patient survival,” explains Dr. López-Bigas, ICREA researcher at IRB Barcelona.

Five factors, five keys to immunotherapy

The five factors identified are: tumour mutational burden; effective T cell infiltration; the activity of transforming growth factor beta (TGF-β) in the tumour microenvironment; previous treatment received by the patient; and tumour proliferative potential. These factors in different types of cancer are associated with the response to CPIs and have been validated by the authors in six independent cohorts, covering a total of 1,491 patients.

These five factors provide a framework for organising the vast current knowledge about biomarkers of immunotherapy response. “So far, many studies have focused on identifying and reporting individual biomarkers, but our results suggest that many of these biomarkers might be different versions of the same underlying factors,” says Dr. González-Pérez.

» For further information: IRB Barcelona website [+]
» Reference article: Usset, J., Rosendahl Huber, A., Andrianova, M.A. et al. Five latent factors underlie response to immunotherapy. Nat Genet (2024). DOI: 10.1038/s41588-024-01899-0