Investigators from Cedars-Sinai Cancer have discovered that cancerous tumors called soft-tissue sarcomas produce a protein that switches immune cells from tumor-attacking to tumor-promoting. The study, published today in the peer-reviewed journal Cell Reports, could lead to improved treatments for soft-tissue sarcomas.
The researchers focused on the tumor microenvironment — an ecosystem of blood vessels and other cells recruited by tumors to supply them with nutrients and help them survive.
“Tumors also recruit immune cells,” said Jlenia Guarnerio, PhD, a research scientist with Cedars-Sinai Cancer, assistant professor of Radiation Oncology and Biomedical Sciences and senior author of the study. “These immune cells should be able to recognize and attack the tumor cells, but we found that the tumor cells secrete a protein that changes their biology, so instead of killing tumor cells they actually do the opposite.”
Soft-tissue sarcoma is a rare type of cancer that forms in the muscle, fat, blood vessels, nerves, tendons and joint lining. It most commonly occurs in the arms, legs and abdomen, and kills more than 5,000 people in the U.S. each year, according to the American Cancer Society.
In comparing samples of a variety of soft-tissue sarcomas in humans and laboratory mice, Guarnerio and her team noted that most of these tumors have an abundance of immune cells called myeloid cells in their microenvironment.
“It was striking that such a large percentage of the immune cells were myeloid cells, and we thought that since they obviously weren’t killing the tumor cells, they must be doing something to promote tumor growth,” said Stephen Shiao, MD, PhD, division director of the Division of Radiation Biology, co-leader of the Translational Oncology Program and a co-author of the study. “And indeed, our analysis of tumor samples showed that many of the myeloid cells had adopted a tumor-promoting function.”
To find out what was causing this change, investigators examined the proteins secreted by the tumor cells and the receptors on the surface of the myeloid cells — the elements cells use to communicate. “We examined the cross-talk between these two populations of cells,” Guarnerio said. “We found that the tumor cells expressed high levels of a protein called macrophage migration inhibitory factor [MIF], and that the myeloid cells had receptors to sense the MIF proteins. This makes them switch their biology and promote, rather than block, tumor growth.”
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