““Oncometabolite” Neutralizes Immune Cells Near Tumors was originally published by the National Cancer Institute.”
November 18, 2022, by Carmen Phillips from the National Cancer Institute
Credit: iStock
It’s no secret that mutations in specific genes can cause normal cells to become cancerous and supercharge their ability to form tumors.
A new study by researchers at Harvard Medical School suggests that one of these mutations, in the IDH1 gene, may do more than cause cancerous changes inside cells. A molecule called D-2HG that is released in large amounts by cancer cells with IDH1 mutations acts as a type of force field by neutralizing nearby immune cells, they found.
As cells produce the energy they need to function, a process called metabolism, they create molecular products called metabolites. D-2HG is a metabolite that is only made by cells with mutations in IDH genes, which includes IDH1 and IDH2. Metabolites like D-2HG that are found at higher levels in cancer cells than normal cells—and presumed to fuel cancer in some way—are often called oncometabolites.
Conducted largely using cells in lab dishes, the study showed that after being released by cancer cells into their surrounding environment, D-2HG is quite busy. First, it is readily taken up by immune cells called T cells. And once inside, it disrupts the T cells’ ability to kill cancer cells.
Results from the NCI-funded study were published September 29 in Science.
More studies are needed to confirm the extent to which these effects of D-2HG are seen in people whose tumors have mutations in IDH genes, said the study’s senior investigator, Marcia Haigis, Ph.D., a professor of cell biology at Harvard Medical School. Further research can also help determine if blocking the activity of D-2HG might be a new way of treating these cancers, Dr. Haigis continued.
As for this current study, she said, the results bring into focus a more universal idea about cancer cell metabolism and the immune system.
“We know that in tumors there are thousands of metabolites,” she said. It’s quite likely that other metabolites in and around tumors “may impact T cells … and affect the immune system’s ability to control tumors.”
