A new multi-omics study has identified three molecular subtypes of colorectal cancer (CRC), with one subtype, known as CS3, showing strong potential for predicting response to immunotherapy. Researchers analyzed genetic, epigenetic, and molecular data and found that CS3 tumors are highly mutated, genomically unstable, and rich in immune activity.
Importantly, CS3 includes a subset of microsatellite-stable (MSS) tumors with extremely high mutation rates that may benefit from immune checkpoint inhibitors, even though they would not normally qualify for such treatment under current guidelines. The subtype was associated with elevated immune markers, high tumor mutation burden, and increased expression of immune checkpoint proteins.
The team also developed an 11-gene signature to identify high-risk patients and predict outcomes. This tool may help doctors better select patients for immunotherapy and identify alternative targeted treatments for those with resistant disease. The findings could expand precision medicine approaches and improve treatment options for colorectal cancer patients.