In January 2025, researchers from the Francis Crick Institute published a study in Cancer Cell identifying the protein CD74 as a predictive marker for immunotherapy response in bowel cancer patients, regardless of subtype. Bowel cancer, the UK’s fourth most common cancer and second leading cause of cancer-related deaths, is categorized into two subtypes: deficient mismatch repair (dMMR), where DNA repair proteins are lacking, and proficient mismatch repair (pMMR), where these proteins are intact. While immunotherapy has been effective in approximately half of dMMR cases, pMMR patients, constituting about 90% of all cases, have not been eligible for such treatments. The study found that elevated CD74 levels in tumor samples correlated with positive responses to immunotherapy across both subtypes, suggesting that CD74 could serve as a biomarker to identify pMMR patients who might benefit from immunotherapy.
The research team analyzed the tumor microenvironment and discovered that the presence of three immune cell types—T cells, natural killer (NK) cells, and macrophages—was essential for a favorable immunotherapy response. These cells, when in proximity to cancer cells, produced interferons that activated signaling pathways in macrophages and tumor cells. This immune activation was notably higher in dMMR tumors responsive to immunotherapy; however, some pMMR patients exhibited similar immune signatures. Further investigation revealed that high CD74 expression was associated with this immune-activated environment, indicating its potential as a universal marker for immunotherapy suitability in bowel cancer patients. Implementing CD74 testing could expand treatment options, offering immunotherapy to a broader range of patients beyond the current dMMR subgroup.
