Soft-tissue sarcoma is a cancer that occurs in muscles, connective tissue, fat, blood vessels, nerves, tendons, and joint linings.
By body part, it occurs frequently in the order of limbs, abdominal cavity posterior wall, intestines, body cavity, and head and neck.
Although classified as a rare cancer, soft tissue sarcoma kills more than 5,000 patients in the United States each year. In particular, synovial sarcoma metastasizes to the lungs and the prognosis is poor.
A specific protein produced by soft tissue sarcoma has been found to act as a switch that blocks the attack of immune cells.
When this protein, which inhibits the movement of macrophages, is expressed, immune cells that originally attacked cancer cells actually helped the growth of cancer cells.
The results of this study, conducted by scientists at the Cedars-Sinai Medical Center in Los Angeles, USA, were published as a thesis in the open access journal ‘Cell Reports’ on the 21st (local time).
The research team found this protein in the ‘tumor microenvironment’.
In order for cancerous tumors to survive and grow for a long time, they must absorb much more nutrients than normal cells.
To this end, cancer tumors make new blood vessels and attract other cells to the environment, which is called the tumor microenvironment.
During comparative analysis of soft tissue sarcoma samples from human and mouse models, an unusual phenomenon caught attention.
The microenvironment of most tumor samples was exceptionally high in myeloid cells.
For example, among the immune cells that tumors have attracted to the microenvironment, bone marrow cells have the highest share.
Bone marrow cells refer to young cells of the granulocyte family that occur in the bone marrow.
It didn’t make sense for cancerous tumors to attract immune cells that could attack them.
However, in further experiments, conversely, many bone marrow cells functioned to promote tumor growth.
The research team carefully examined the proteins secreted by the tumor and receptors on the surface of the bone marrow cells to determine the cause of the bone marrow cells having this function.
By analogy, it is like overhearing what kind of talk (signal) the cancer cells and bone marrow cells exchange.
Unexpectedly, a large amount of ‘macrophage migration inhibitory factor’ (MIF) was expressed in tumor cells, and MIF-sensing receptors were present on the surface of bone marrow cells.
This means that the bone marrow cells can receive messages from the tumor cells to keep them out of access.
This MIF was the ‘molecular switch’ the research team was looking for.
When this switch is on, the bone marrow cells take the lead in helping cancer cells instead of attacking them.
However, tumors grown with cancer cells that do not express MIF were weak against attack by bone marrow cells.
These tumors were easily penetrated by bone marrow cells, which inhibited tumor growth.
“This means that bone marrow cells can directly attack tumors or activate immune cells such as T cells,” said Illenia Guarnerio, associate professor of radiation oncology, who is the corresponding author of the paper.
Not surprisingly, this finding could help develop new treatments for soft tissue sarcoma.
For example, scientists say that developing a drug that blocks MIF expression in cancer cells and administering it in parallel with existing anticancer drugs could be a promising treatment.
For soft tissue sarcoma, which recurs after treatment and becomes more aggressive, it is difficult to see the effect even with existing anticancer drugs.
It is also noteworthy that this study focused on sarcoma, a rare cancer type.
So far, cancer biology and immuno-oncology research has focused on a common type of cancer (carcinoma).
Carcinoma refers to cancer caused by DNA damage of cells in epithelial tissue, and sarcoma arises from transformed cells of mesenchymal origin.
Professor Guarnerio said, “For carcinoma, the types of immune cells that penetrate the tumor and how the cancer cells and immune cells interact have been studied in detail, but there is almost no research on sarcoma.” We need to deeply understand the roles of T cells and B cells,” he said.