Tracking molecular malfunctions in metastatic colorectal cancer to find new avenues for treatment
Researchers at Hokkaido University, in collaboration with an international team of scientists led by the University of South Florida Health and Tampa General Hospital, have uncovered an important mechanism behind immune evasion in metastatic colorectal cancer (mCRC). Their findings challenge a 30-year-old theory about cancer.
Researchers at Hokkaido University and the University of South Florida Health have uncovered how metastatic colorectal cancer evades the immune system, challenging a 30-year-old theory. The traditional rheostat model suggested that elevated sphingosine-1-phosphate (S1P) promotes tumor growth, while higher ceramide levels trigger cell death.
However, this study found that the imbalance occurs within the tumor microenvironment, not within the cancer cells themselves. S1P creates a local biochemical barrier that prevents immune cells from attacking the tumor, while reduced ceramide levels contribute to ongoing inflammation. This creates a hostile environment that blocks killer immune cells, preventing them from reaching and destroying the tumor.
The study identified a specific three-gene signature associated with aggressive cancer, poor survival, and resistance to immunotherapy. Blocking S1P/S1PR3 in lab experiments restored cytotoxic T-cell infiltration, suggesting that targeting this pathway could make immunotherapy effective for advanced colorectal cancer patients.
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