Researchers at the University of Calgary have reported what could be a major breakthrough in the treatment of colorectal cancer: removing a single gene may render tumor cells visible to the immune system and dramatically improve the effectiveness of immunotherapy.
The study, published in the journal Cell Reports Medicine, was led by Dr. Arshad Ayyaz from the Department of Biological Sciences and the Arnie Charbonneau Cancer Institute.
According to the researchers, immunotherapy—which trains a patient’s immune system to recognize and destroy cancer cells—has shown remarkable success in several types of cancer. However, in colorectal cancer, it is effective in only about 15% of cases.
The team compared the genetic characteristics of tumors that respond to treatment with those that remain resistant and identified a previously unknown mechanism of immune evasion.
In treatment-resistant tumors, the scientists discovered a protein that essentially misleads the immune system, preventing it from recognizing the cancer. The researchers describe this mechanism as a form of tumor “camouflage.”
“We asked ourselves: what would happen if we stopped the production of this protein?” Ayyaz explained.
Using genetically engineered cancer cells, the researchers switched off the gene responsible for producing the protein. Once the gene was disabled, tumor cells became detectable by the immune system.
When combined with immunotherapy in mouse models, the approach led to complete tumor elimination, achieving a 100% response rate.
“At first, I could hardly believe it. One gene turned off—and the result was completely clear,” the researcher said.
Even without additional immunotherapy, tumors shrank because they lost their ability to hide from the body’s natural immune defenses.
The authors emphasize that the findings are still at the preclinical stage, and it may take years before the strategy reaches clinical practice. Nevertheless, the approach could potentially be applicable to other solid tumors as well, including pancreatic and lung cancers.
