How do the mechanical properties of a tumour influence its ability to evade the immune response? Research published in the prestigious journal ‘Cancer Discovery’ presents promising results. Among the co-authors of the paper entitled ‘Extracellular matrix stiffness controls Transposable Elements through Pin1 to promote immune evasion in breast cancer’ is dr Paulina Nastały from the Department of Translational Oncology at the Intercollagiate Faculty of Biotechnology UG and MUG.

The research, led by prof. Giannino Del Sala from the International Centre for Genetic Engineering and Biotechnology at the University of Trieste and the Institute of Molecular Oncology in Milan, reveals a new mechanism linking the mechanical properties of the tumour microenvironment to its ability to evade the immune response.

The researchers have demonstrated that increased stiffness of the extracellular matrix promotes the accumulation of the Pin1 protein in the cell nucleus, which leads to the silencing of transposable elements and the suppression of the cGAS-STING pathway. As a result, cancer cells become less recognisable to the immune system.

Importantly, inhibiting Pin1 activity using drugs already in clinical use - all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) - enhanced the efficacy of immunotherapy in preclinical models of breast cancer.

This discovery opens up new avenues in the search for ways to overcome tumour resistance to immunotherapy. It suggests that not only intracellular processes, but also the mechanical properties of the surrounding tissues and chromatin organisation play a role in regulating the anti-tumour response. However, the potential for using this strategy in the treatment of patients requires confirmation in further studies, including clinical trials.

Cancer Discovery is a prestigious international scientific journal, published monthly by the American Association for Cancer Research (AACR). It features advances in cancer research and the results of clinical trials. Its Impact Factor (JIF) is 29.5.

Publication: “Extracellular matrix stiffness controls Transposable Elements through Pin1 to promote immune evasion in breast cancer”, Cancer Discovery, 2026.

DOI: 10.1158/2159-8290.CD-25-0942.