Soft-tissue sarcomas are extremely difficult to treat. One reason is that knowledge of the sarcoma microenvironment composition is limited. However, successful treatment for some solid tumors that target the tumor microenvironment may not be able to.
Researchers have used a single-cell RNA-seq to distinguish the immune structure of an undifferentiated pleiomorphic sarcoma mouse model. They have discovered that soft-tissue sarcomas are developing a protein that switches immune cells from tumor-attacking to tumor-promoting. This results might lead to improved therapies for soft-tissue sarcomas.
Cell Reports discusses the central role of tumor-expressed MIF in shaping macrophage heterogeneity in the single-cell RNA sequence.
Tumors also recruit immune cells, according to Ilenia Guarnerio, a research scientist at Cedars-Sinai Cancer and an assistant professor of radiation oncology and biomedical sciences. The tumor cells should be able to recognize and attack the tumor cells, but we found that the tumor cells secrete a protein that alters their biology, thus instead they actually do the opposite.
The soft-tissue sarcoma is a rare form of cancer that forms in the muscles, muscles, muscles, muscles, and joint lining. It most commonly occurs in the arms, legs, and abdomen, and kills more than 5,000 people every year, according to the American Cancer Society.
The researchers used single-cell RNA-seq to investigate the immune composition of a pleiomorphic sarcoma mouse model in a variety of soft tissues. Guarnerio and her team tested the possibility that most of these tumors have an abundance of myeloid cells in their microenvironment.
We thought that because they didn''t kill the tumor cells, they must be doing something to improve tumor growth, according to Stephen Shiao, the division director of radiation biology and co-leader of the Translational Oncology Program. Indeed, our tumor samples showed that many of the myeloid cells had adopted a tumor-promoting strategy.
Investigators examined the proteins secreted by the tumor cells and the receptors on the surface of the myeloid cells to investigate what caused this change. Several studies have shown that these tumor cells had high levels of a 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.
Myeloid cells were able to penetrate tumors when investigators generated tumors from cancer cells that didn''t express MIF.
This implies that myeloid cells might have directly attacked the tumors, or that they might have activated other immune cells, such as T cells, to attack the tumors. According to Guarnerio,
Researchers believe this information will be used to develop novel therapies against soft-tissue sarcoma. A medication designed to stop cancer cells fromexpressing MIF might be tested in combination with existing therapies, for example, to see if it improves outcomes for patients.
The majority of research in cancer biology and immunotherapy has focused on carcinoma, the most common type of cancer. However, much research has been done to identify which immune cells infiltrate these tumors, and how carcinoma cells interact with immune cells, but there is still no research on these sarcomas. We need to continue our research so that we understand the roles of many other cellsT cells and B cells, for example.