Protein level predicts immunotherapy response in bowel cancer
24 January 2025
Research involving UCL scientists has shown that the amount of a protein called CD74 can indicate which people with bowel cancer may respond best to immunotherapy.

If integrated into the clinic, testing for this protein could potentially allow hundreds of previously ineligible patients to benefit from this type of treatment.
Bowel cancer is the fourth most common cancer in the UK, and the second most common cause of cancer death. The disease falls into two types: one where proteins that repair errors in DNA are missing or deficient (the deficient subtype), and one where this machinery is intact (the proficient subtype).
Cancer immunotherapy drugs, which boost the immune system to fight the tumour, have revolutionised the treatment of the deficient subtype of colorectal cancer.
However, these drugs only work in about half of these individuals, and people with the proficient subtype, who represent ~90% of all cases, currently aren’t eligible for immunotherapy treatment.
In the study, led by the Francis Crick Institute and Barts Cancer Institute, published in Cancer Cell, researchers investigated why immunotherapy only works for certain people with bowel cancer, and how we might increase the number of patients who can benefit from this treatment. They found that the levels of expression of a protein called CD74 can predict response to immunotherapy, independent of subtype.
"In the study, we identified two colorectal cancer (CRC) subtypes—IFN-high and IFN-low—based on seven gene signatures. The IFN-high subtype showed better responses to immune checkpoint immunotherapy. Additionally, we found that tumors responding to these immunotherapy drugs produced more of a protein called CD74, regardless of their genetic status," said Manuel Rodriguez Justo, Professor of Oncopathology (UCL Cancer Institute) and one of the study authors. "If these results are replicated in other tumour types, potentially CD74 could become a biomarker to predict response to immunotherapy, independently of the microsatellite stability status.”
Francesca Ciccarelli, Professor of Cancer Genomics (Queen Mary University of London’s Barts Cancer Institute) and corresponding author, said: “Immunotherapy drugs can be hugely successful for people with bowel cancer, but currently the majority of patients can’t be prescribed these drugs and, even when patients are eligible, we don’t know upfront who will respond.
“Our work suggests that testing for CD74 levels – which signal that the immune system is ‘just right’ to fight the tumour – could widen access to immunotherapy. This could revolutionise treatment for a sizeable fraction of people with the proficient bowel cancer subtype, which is a large number of patients across the UK in real terms. It could also be used to identify people with the deficient subtype who won’t respond, saving them from experiencing side effects unnecessarily.”
The research team are now working with Cancer Research Horizons to develop the findings into a test that can work in the clinic. They will also research why macrophages and tumour cells overexpress CD74, and whether this marker is present in other types of cancer.
Further information
- Research paper: A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer. Cancer Cell
- Manuel Rodriguez-Justo profile
- Francesca Ciccareli profile
- Source: Francis Crick Institute and Barts Cancer Institute
- CRUK bowel cancer statistics
- Main image: The deficient subtype (left, IFN-high ) and proficient subtype (right, IFN-low) with different populations of immune cells. CD74 expression is highest in tumours with a particular type of immune environment, which is more likely to be in the deficient subtype. - Acha-Sagredo, A. Andrei, P. and Clayton, K. et al. (2025). Cancer Cell.