A recent study, conducted in collaboration between the Medical University of Vienna and IEO, shed light on how age can affect the composition of the tumour microenvironment and the response to treatments in preclinical models of triple-negative breast cancer. The research results have just been published in the journal Cell Death & Differentiation.
Researchers analysed the efficacy of a therapy based on a combination of immunotherapy and drugs that activate the immune system (currently under clinical evaluation as part of the Azalea study), against tumours developed in two groups of rodents: young, equivalent to human puberty, and adults, corresponding to about 40 years of age in human.
The results showed that while therapy works similarly in the two groups, significant differences are present in the tumour microenvironment, i.e., all those structures (including the nearby non-tumoral tissues, and blood vessels) that surround the tumour and can influence its growth.
“In adults, a reduction of specific immune cells crucial in fighting cancer, such as CD4+ T cells and NK cells, was observed, while memory B cells were more abundant. In addition, the extracellular matrix, a typical element of connective tissues that provides structural support to the tumour, showed less collagen and a different organization than in young individuals. This feature could enhance tumour aggressiveness and alter the response to therapies other than the one considered in our study,” explain the first authors of the study, Stephan Grüner (a doctoral student in the Cancer Genomics Laboratory at the Medical University of Vienna), Paolo Falvo, and Stefania Orecchioni (both researchers in the IEO Hematoncology Laboratory).
“Our study suggests the importance of considering age as a key criterion of preclinical research for new anticancer therapies. Indeed, the results of our study indicate that preclinical models based solely on young individuals may not accurately represent the reality of adult patients. After all, we know that cancer incidence increases with age, paralleling physiological changes in our bodies and their functions. We have therefore long hypothesized that preclinical studies should take age into account. We hope that many more studies like ours will follow. Considering age in research models could indeed improve the prediction of treatment efficacy and the development of more targeted therapies for cancer patients, even and especially those affected by the most aggressive and least treatment-responsive forms,” comment Iros Barozzi, director of the Cancer Genomics Laboratory and professor at the Medical University of Vienna, and Francesco Bertolini, director of the IEO Hematoncology Laboratory Division, who co-coordinated the study.
Publication:
Paolo Falvo, Stephan Gruener, Stefania Orecchioni, Federica Pisati, Giovanna Talarico, Giulia Mitola, Davide Lombardi, Giulia Bravetti, Juliane Winkler, Iros Barozzi & Francesco Bertolini.
Age-dependent differences in breast tumor microenvironment: challenges and opportunities for efficacy studies in preclinical models.
Cell Death & Differentiation, 2025. DOI: 10.1038/s41418-025-01447-1;
https://www.nature.com/articles/s41418-025-01447-1