1.From Growth Signal to Immune Brake
The study focuses on the so-called epidermal growth factor receptor EGFR, which sits at the surface of many cells and is responsible for cell growth and cell-division signalling. It is also known for being an important factor in the growth of cancer cells and is already a target of various cancer therapies, as EGFR levels are elevated in tumour cells. The team led by study director Maria Sibilia from the Center for Cancer Research at the Medical University of Vienna and the Comprehensive Cancer Center of Medical University of Vienna and Vienna General Hospital (AKH Wien) has now shown that EGFR also plays a crucial role in certain immune cells, where the receptor helps to suppress the immune response against the tumour.
The results thus provide a new starting point for potential combination therapies.
“Our results show that it is not only the cancer cells themselves that determine the success of a therapy. Certain immune cells in their environment can also significantly slow down the defence against the tumour. If we switch off the EGFR signal in these cells, part of this immune brake is removed and immunotherapy can be significantly more effective,” explains Sibilia.
2.Why Checkpoint Inhibitors Fail in Colorectal Cancer
This finding is particularly relevant for the large group of patients with metastatic colorectal cancer in whom so-called checkpoint inhibitors have so far been largely ineffective. In the preclinical mouse model used here, switching off the EGFR signalling pathway in certain myeloid immune cells was able to enhance the immune response against liver metastases. In combination with immunotherapy targeting PD-L1, the development of liver metastases was prevented.
EGFR sits at the top of a signalling chain that runs through RAS and RAF into the cell nucleus, where it drives growth and division. If RAS or RAF is mutated, that chain is switched on permanently below the receptor, so blocking the receptor no longer interrupts anything. This is why anti-EGFR antibodies such as cetuximab and panitumumab are given only to patients whose tumours carry unmutated RAS and RAF.
3.Outlook: What Would Have to Follow
In the future, it could be investigated whether targeted manipulation of EGFR in these immune cells can help make previously therapy-resistant colorectal cancer metastases more susceptible to immunotherapies. However, further research and clinical trials are necessary before a new treatment strategy can be developed.
The study was conducted under the leadership of the Center for Cancer Research at the Medical University of Vienna and the Comprehensive Cancer Center of the Medical University of Vienna and Vienna General Hospital (AKH Wien) in collaboration with the Institute for Research in Biomedicine (IRB) in Barcelona.
Sources: Moreno-Viedma V., Adachi-Fernandez E. et al. (2026), Absence of EGFR signalling in granulocytic cells relieves immunosuppression sensitising CRC metastases to immune checkpoint therapy, Cell Death & Differentiation. DOI: 10.1038/s41418-026-01828-0 · Press release by the Medical University of Vienna, AKH Wien and the Comprehensive Cancer Center Vienna, 19 August 2026.
The quote from Maria Sibilia is taken from the press release of the Medical University of Vienna, AKH Wien and the Comprehensive Cancer Center Vienna (19 August 2026) and was translated from the German.