SAN DIEGO — Malignant tumors thrive in part by suppressing the immune system. A team led by Salk Institute scientists reports discovering one important way this takes place.
Moreover, the scientists say they have restored the immune response, inhibiting tumors in mice. They have also found evidence that the mechanism is at work in cancer patients.
A study on the findings was published in Nature Cell Biology.
Tumors make two small molecules of RNA called micoRNAs to suppress the immune response, the study said. These microRNAs turn off a sensing system called cGAS that detects the abnormal presence of DNA and alerts the immune system.
Free DNA is normally absent from cells, being bound up either in the nucleus or in mitochondria. So its presence indicates something is wrong. The cGAS system detects viral DNA, and DNA released from destroyed mitochondria.
In mice, blocking these microRNAs, called miR-25 and miR-93, slowed tumor growth. Growth didn’t slow in mice with deficient immune systems, pointing to an immune response as the cause.
Patients with invasive breast cancer were also studied for levels of these microRNAs. Those with higher levels had poorer survival rates than those with lower levels.
Immune cells patrol the body, searching for pathogens and for damaged cells. When they’re detected, other immune cells are called out to destroy them. But cancer cells managed to evade this response.
Several different mechanisms are involved in this process, and the study pointed to one of them, said Omid Hamid, M.D., director of the Melanoma Center at The Angeles Clinic and Research Institute, an affiliate of Cedars-Sinai.
“I think that it just confirms what we’ve always known, that there are multiple different mechanisms for immune suppression,” Hamid said.
The big question is whether this mechanism can be targeted in patients, and that isn’t clear, Hamid said.
“I think it’s possible,” Hamid said. D etecting the microRNAs could be used to evaluate patient prognosis, he said.
