Paulina Nastały, M.D., Ph.D. from the Department of Translational Oncology at the Intercollegiate Faculty of Biotechnology UG&MUG is a co-author of a scientific paper published in the prestigious Cancer Discovery journal (Impact Factor: 29.5), published by the American Association for Cancer Research (AACR). The study, entitled Extracellular matrix stiffness controls Transposable Elements through Pin1 to promote immune evasion in breast cancer, presents findings on the mechanisms which enable breast cancer cells to evade the immune response.
The research, led by Prof. Giannino Del Sal, affiliated with the International Centre for Genetic Engineering and Biotechnology (ICGEB), the University of Trieste and IFOM in Milan, identified a novel mechanism linking the mechanical properties of the tumour microenvironment to its ability to evade immune recognition.
The researchers demonstrated that increased stiffness of the extracellular matrix, the structure surrounding tumour cells, promotes the accumulation of the Pin1 protein in the cell nucleus. This leads to the silencing of transposable elements and reduced activation of the cGAS–STING signalling pathway, which plays an important role in initiating immune responses. Consequently, tumour cells become less readily recognised by the immune system.
Another important aspect of the study was investigating whether this mechanism could be overcome. In preclinical models of breast cancer, inhibition of Pin1 activity using all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) enhanced the effectiveness of immunotherapy.
The findings suggest new avenues for developing therapeutic strategies which could help overcome tumour resistance to immunotherapy. They also highlight the importance of the mechanical properties of the tumour microenvironment and the regulation of genetic element activity in shaping antitumour immune responses. However, the potential clinical application of the proposed strategy requires further investigation in clinical studies.
