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New biomarker predicts success of immunotherapy for kidney cancer
Last reviewed: 02.07.2025
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Immunotherapy increases survival in kidney cancer, but it is not suitable for all patients. A research team from Leuven has developed a new method for predicting who will benefit from this treatment. A team led by Francesca Finotello from the Computational Biomedicine Group at the University of Innsbruck also contributed to the study.
Their work, published in the journal Nature Medicine, opens new avenues to more effective treatments.
Every year in Austria, around 1,300 people are diagnosed with kidney cancer. Thanks to immunotherapy, survival rates for metastatic kidney cancer have increased significantly: more than half of patients survive more than five years after diagnosis, compared to 10% in the past. Unfortunately, the innovative treatment does not work for all patients.
To understand the reasons for this variation in the effectiveness of immunotherapy and in the hope of better predicting who will benefit from the treatment, the Leuven research team conducted a large retrospective study. They analyzed many samples from kidney cancer patients treated with immunotherapy at UZ Leuven over the past ten years.
Molecular signature Researcher and oncologist Dr Lisa Kingett and postdoc Stefan Naulaerts explain: “We examined both tumour biopsies and blood samples using cutting-edge laboratory techniques. Using machine learning, we combined gene expression in the tumour with hereditary characteristics of the patients’ immune system, in particular the HLA genes, which have hundreds of variations depending on the individual.
This approach allowed us to discover a “molecular signature” that showed a clear association with clinical response and survival. We further confirmed this association in independent samples from over 1,000 kidney cancer patients from other international studies.”
Laboratory tests also showed that a successful response to immunotherapy was associated with good interaction between two types of immune cells, namely CD8+ T cells and macrophages.
Dr Francesca Finotello from the Department of Molecular Biology at the University of Innsbruck and the Digital Science Centre (DiSC) adds: “We integrated and analysed big data from The Cancer Genome Atlas (TCGA) project to link this new molecular signature to the mutational landscape of tumours, demonstrating that it provides additional information regarding the genetic background of cancer cells, effectively capturing their interactions with the immune system.”
Professor Abhishek D. Garg from KU Leuven says: “Previously, researchers mainly studied immune cells at the level of individual cell types, which led to simplified biomarkers. As a result, we thought that macrophages were ‘bad’ for immunotherapy. With this study, we have shown that the interaction between different types of immune cells in a specific spatial context is more important in the fight against kidney cancer.”
Professor Benoit Böselink, a medical oncologist at UZ Leuven, says: "In the future, we hope to use our method as a biomarker to predict which patients will benefit from immunotherapy. The new insight that the interaction between certain T cells and macrophages is important for the success of immunotherapy opens up interesting avenues for future treatments.
We are now developing new clinical trials of combination therapies to stimulate both cell types and improve their work together, which may be more effective than current treatments.”