How salmonella helps kill cancer cells

Bacterium stimulates the immune system to ‘see’ tumors, could lead to vaccine

When a bad bacterium infects tumor cells, it can signal the body to fight the deadliest form of skin cancer.

Scientists already knew that diarrhea-causing Salmonella typhimurium helps the immune system recognize melanoma, but a paper in the Aug. 11 Science Translational Medicine shows how. The finding may point to a new human vaccine for melanoma and possibly other kinds of cancer.

“In combination with other therapies, it could improve survival,” says tumor biologist Meenhard Herlyn of the Wistar Institute in Philadelphia. But melanoma is such a complex cancer that a vaccine probably couldn’t cure the disease permanently, adds Herlyn, who was not involved with the study.

When Salmonella was injected into mouse melanoma tumors, those tumors shrank, as did untreated tumors in other parts of the body. Experiments showed that the process relied on the presence of a protein channel called connexin 43 on the surface of melanoma cells.. That protein channel allows the cells to connect to similar channels in immune cells, forming ‘gap junctions’ that allow the two cells to share their contents.

Salmonella got into the tumor cells and caused them to rev up production of the channel-forming protein. Those protein channels connected with immune cells and allowed bits of tumor proteins to pass through.

The immune cells, called dendritic cells, then displayed the bits of tumor protein on their own surfaces. In doing so, they activated other immune cells to find and kill tumor cells bearing those same proteins.

“We now have a ‘gun’ to kill specifically tumor cells,” says lead study author Maria Rescigno, an immunologist from the European Institute of Oncology in Milan. “We are inducing an immune response to that ‘fingerprint’ which is specific for the tumor.”

Rescigno and her team think they could use the new knowledge about how the salmonella treatment works to produce human vaccines against melanoma and other types of cancers. Her team successfully vaccinated mice against melanoma by injecting them with the bacteria-treated melanoma cells.

Instead of injecting patients with salmonella, researchers could instead teach the patient’s own immune cells to recognize tumors in the lab. By mixing the patient’s tumor cells with Salmonella and then the patient’s own immune cells, those immune cells would learn to target tumor cells specifically. Those “educated” immune cells could then be injected back into a patient’s body to attack the cancer.

Melanoma is believed to be influenced by genetics and also to be caused by sun exposure. Once the cancer has spread to other body organs, the five-year survival rate is below 15 percent and there is no cure. Like other cancers, one way melanoma hides from the immune system is by removing membrane proteins on its cell surfaces that would otherwise connect with the body’s immune system.

Rescigno is already in the process of getting authorization from the Italian Ministry of Health to start human trials of a vaccine. We hope by May or June next year to have the protocol in the clinics for treating melanoma patients,” she says.

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