The immune system is programmed to recognize foreign bodies as potentially dangerous, promptly removing them before the intruders can cause the body harm. However, the immune system “tolerates” certain foreign tissues, such as a fetus developing in the womb, for example.
For these nine months, the maternal and fetal immune systems coexist in a symbiotic relationship, with soluble and cell-surface molecules produced by the fetus thought to facilitate this mutual tolerance by suppressing the maternal immune system.
In a scientific study published in the journal Cell, researchers identified that liver tumor cells can shield themselves from the immune system by disguising themselves as fetal cells and employing similar immunosuppressive tactics. This strategy allows the cancer cells to thrive and spread without interference.
Immunologists mapped the genetic profiles of around 200,000 individual human liver cells that were extracted from both developing fetuses and hepatocellular carcinomas, a deadly form of liver cancer. They used single-cell RNA sequencing, a technique that allowed the scientists to identify parallels in the gene expression profiles between the two liver cell types.
The research team found that like fetal cells, the liver cancer cells were able to keep immune cells at bay by activating specific cell signaling pathways, such as VEGF signaling. This had the domino effect of triggering the Notch-Delta pathway in monocytes, making them differentiate into macrophages with immunosuppressive phenotypes.
Since 1980, liver cancer incidences have more than tripled, with an estimated 42,230 adults in the United States diagnosed with the disease annually. These and other studies to understand the molecular mechanisms orchestrating liver cancer progression pave the way towards effective treatments to combat the disease.
“Our results unravel a previously unexplored onco-fetal reprogramming of the tumor ecosystem, provide novel targets for therapeutic interventions in HCC, and open avenues for identifying similar paradigms in other cancers and disease,” wrote the authors.