Lung cancer: new mechanism of resistance to immunotherapy discovered
At the centre of the research is the hMENA protein: these are non-tumour cells but make the tumour more aggressive and resistant to treatment
Key points
Non-small cell lung cancer can actively build an environment that protects it from the immune system, reducing the effectiveness of immunotherapies. This is the finding of a study co-ordinated by researchers at the Regina Elena National Cancer Institute (IRE), the results of which were published in the Journal for ImmunoTherapy of Cancer.
'At the heart of the research,' the Institute explains, 'is the hMENA protein that regulates a group of cancer-associated fibroblasts. These are non-cancerous cells, but they can make the tumour more aggressive and resistant to treatment'. The data also showed 'a vicious circle of mutual reinforcement between TGF-β and hMENA: each protein keeps the other active, consolidating a tumour-friendly microenvironment over time'.
Working on new treatment options
The research group of the IRE Immunology and Immunotherapy Unit, which identified the hMENA protein several years ago, is now engaged in the development of pharmacological strategies to block its action in cancer and drug resistance. "Understanding how the tumour builds its defence environment, which allows it to grow and escape the control of the immune system, is one of the most important challenges in oncology today," explains Paola Nisticò, head of the Immunology and Immunotherapy Unit at the Regina Elena Institute. - The results of our study represent an important step in this direction, opening the way to new therapeutic strategies'.
The impact of non-small cell lung cancer
Lung cancer is the third most frequent type of cancer in Italy and when it is diagnosed at an advanced stage, the chances of cure are significantly reduced. Non-small cell lung cancer, which accounts for around 85% of cases, is the most common form. In recent years, immunotherapy has revolutionised the treatment scenario, but not all patients respond to these innovative treatments. Even among those whose tumours are initially sensitive, resistance often develops over time. Understanding the mechanisms that limit the effectiveness of these treatments is therefore a clinical and scientific priority.
The tumour shapes the environment
Data from the new study by the Regina Elena Institute showed that the tumour does not grow in isolation, but also actively shapes its surroundings. In this context, fibroblasts around the tumour, driven by the hMENA protein, help to hinder the immune response and at the same time directly influence the tumour cells. The cancer cells thus acquire characteristics that make them more mobile and invasive, promoting disease progression.
