Single-Cell RNA-Seq of a Soft-Tissue Sarcoma Model Shows Importance of Tumor-Expressed Proteins

In a recent study, researchers concentrated on the tumor microenvironment, an ecosystem of blood vessels and other cells that tumors attract to provide them with nutrients and aid in survival. These immune cells ought to be capable of identifying and eliminating cancerous cells. A protein secreted by tumor cells alters their biology, preventing them from destroying tumor cells as they would otherwise.

MIF Silencing

MIF Silencing. Credit: Cell Reports

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An uncommon soft-tissue sarcoma develops in blood vessels, nerves, tendons, muscle, fat, and joint lining. According to the American Cancer Society, it most frequently affects the arms, legs, and abdomen and claims the lives of over 5,000 Americans annually.

There are currently no effective therapeutic means for recurrent and aggressive soft tissue sarcomas. The sarcoma microenvironment composition is not fully understood. Interventions on elements of the tumor microenvironment have been studied relatively minimally for many solid tumors.

Role of MIF in sarcoma presenting cells

The immunological structure of a mouse model with sarcoma was determined by RNA sequencing. The findings reveal that the macrophages within the mass of the sarcoma exhibit diverse activation states. Sarcoma cells engage with macrophages that express the CD74 receptor via the pleiotropic cytokine macrophage migration inhibitory factor (MIF). By encouraging the buildup of macrophages with inflammatory and antigen-presenting characteristics, MIF expression is prevented in sarcoma cells, which slows tumor growth.

The researchers found that these tumors have an abundance of immune cells called myeloid cells in their microenvironment when comparing samples of various soft-tissue sarcomas from laboratory mice and humans.

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The fact that a sizable portion of the immune cells were myeloid cells was significant. The myeloid cells were not destroying the tumor cells, therefore must be acting in some way to encourage tumor growth. An analysis of tumor samples shows myeloid cells can promote tumor activity. The tumor cells expressed high levels of the protein MIF. Also, the myeloid cells had receptors to sense the MIF proteins after examining the proteins secreted by the tumor cells and the receptors on the surface of the myeloid cells—the elements cells use to communicate. As a result, they alter their biology and encourage tumor growth rather than preventing it.

In cells that did not express MIF, myeloid cells could enter the tumors and inhibit tumor growth. Thus, myeloid cells can fight tumors or stimulate the attack of cancers by other immune cells, such as T cells.

Clinical significance

Present treatments have failed to control severe and recurrent soft-tissue sarcoma. However, minute soft-tissue sarcoma cases have tried using therapies that target tumor microenvironment elements, despite their promise against numerous solid tumors. This work may open the door for interventions that may be more successful in sarcoma treatment.

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The most prevalent form of cancer, carcinoma, has been the subject of cancer biology and immunotherapy. There has been a lot of research on the immune cells that infiltrate these tumors and the interactions between carcinoma cells and immune cells, but little on sarcomas. The study aimed to comprehend the functions of several other cells, such as T and B cells.


Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity



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