Wounded cancer cells supercharge immune system to destroy tumors
Scientists at MIT have made a discovery that could expand the potential of immunotherapy, enabling it to treat wider variety of cancers. The breakthrough stems from a newfound ability to jump-start the body's immune system with the help of injured cancerous cells, a technique shown to be capable of completely eliminating tumors in mouse models of the disease.
Immunotherapy is a highly promising branch of cancer treatment that seeks to supercharge the body's natural defenses against cancer. There are many possibilities when it comes to how this can be achieved, but the approach pursued by the MIT scientists behind this new study begins with removing tumor cells from the body and then treating them with chemotherapy drugs, at varying dosage levels, and re-inserting them into the tumor.
The idea was to tap into a phenomenon called immunogenic cell death, in which dead or dying tumor cells send out signals that attract attention from the immune system. Delivering these damaged cells back into the tumor along with immunotherapy drugs known as checkpoint blockade inhibitors, which enhance the ability of T cells to attack cancers, was hoped to bring about their swift demise.
But the team's lab dish experiments returned some surprising results. Treating the extracted tumor cells with chemotherapy drugs didn't actually appear to make much of a difference, it was only those subjected to very low doses that yielded the strongest anti-cancer effects.
“This describes a new concept of immunogenic cell injury rather than immunogenic cell death for cancer treatment,” says study author Michael Yaffe. “We showed that if you treated tumor cells in a dish, when you injected them back directly into the tumor and gave checkpoint blockade inhibitors, the live, injured cells were the ones that reawaken the immune system.”
According to the scientists, the chemotherapy drugs that induce the strongest effects are ones that cause DNA damage in the tumor cells, which appears to activate cellular pathways that send out distress signals. With the help of the checkpoint blockade inhibitors, this coaxes the T cells into action and causes them to destroy the injured tumor cells, along with any tumor cells that happen to be nearby.
“Our findings fit perfectly with the concept that ‘danger signals’ within cells can talk to the immune system, a theory pioneered by Polly Matzinger at NIH in the 1990s, though still not universally accepted,” Yaffe says.
The team put their new combination therapy to the test on mouse models of melanoma and breast tumors, and found that tumors were completely eliminated in 40 percent of the mice. When cancer cells were injected into the same mice several months later, the T cells swiftly identified and destroyed them before they could develop into new tumors.
The scientists hope to build on these promising results by testing out the new therapy on patients suffering from tumors that haven't responded to existing immunotherapies. Before that can happen, the team will need to determine which drugs are best suited to which types of tumors, along with the ideal and safe dosage.
The research was published in the journal Science Signaling.