How Does Tumour Tissue Stiffness Influence the Effectiveness of Immunotherapy?

A new study entitled “Extracellular matrix stiffness controls Transposable Elements through Pin1 to promote immune evasion in breast cancer” has been published in the prestigious journal Cancer Discovery (Impact Factor = 29.5), published by the American Association for Cancer Research (AACR). Among the co-authors is Dr Paulina Nastały from the Division of Translational Oncology at the Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk.

The research, led by Prof. Giannino Del Sal from the International Centre for Genetic Engineering and Biotechnology (ICGEB), the University of Trieste, and the FIRC Institute of Molecular Oncology (IFOM) in Milan, reveals a novel mechanism linking the mechanical properties of the tumour microenvironment to the ability of cancer cells to evade immune surveillance.

The researchers demonstrated that increased extracellular matrix stiffness promotes the nuclear accumulation of the Pin1 protein, leading to the silencing of transposable elements and reduced activation of the cGAS–STING signalling pathway. As a result, cancer cells become less visible to the immune system, facilitating immune evasion.

Importantly, inhibition of Pin1 using two drugs already approved for clinical use – all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) – enhanced the effectiveness of immunotherapy in preclinical models of breast cancer.

These findings open new avenues for developing therapeutic strategies to overcome tumour resistance to immunotherapy, highlighting the crucial role of tissue mechanics and chromatin regulation in shaping anti-tumour immune responses. Further clinical studies will be required to determine whether this approach can benefit patients.

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.