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When you remove a bad cancer tumor without showing signs of cancer, it's great news for patients, and scientists now know more why.
They showed that once the bad tumor had been removed successfully, the immune response focused on destroying the tumor cells that it had inevitably sent to the lymph nodes and organs such as the lungs, said Dr. Hasan Korkaya, tumor biologist at Georgia Cancer. Center and Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University.
The fact that metastases did not occur in their model, even months later, indicates that the immune system destroyed the disseminated tumor cells rather than putting them into a waking state, Korkaya and his colleagues reported. newspaper. Nature Communications.
In contrast, when the primary tumor is not completely eliminated, the immune system appears to start supporting the tumor, which regenerates faster and larger than the original mbad, and its disseminated tumor cells survive.
"We wanted to see if we could mimic what was happening in the clinic," says Korkaya, the corresponding author of the study.
Scientists say that what they found in their bad cancer model is probably true for other types of solid tumors that can be removed surgically without any signs of cancer in adjacent tissues.
There has actually been a lot of conflicting information on the subject of allowing lethal metastasis. Retrospective studies in bad cancer patients indicate that complete elimination of the primary tumor improves survival, but murine models indicate that the elimination of the primary tumor actually accelerates growth. tumor cells migrating from the main tumor. Inflammation, a normal response to surgery, has also been shown to promote tumor growth and improve survival.
To better understand what's happening at the molecular level, scientists have used extremely aggressive bad cancer models, such as triple-negative bad cancer in women, and less invasive bad cancer that would allow them to focus on destiny of disseminated bad cancer cells.
In one week, mice of both types had disseminated tumor cells present in lymph nodes draining the bads and lungs, two common sites of bad cancer spread. However, the most aggressive cancer quickly established a growing presence in remote areas. As they expected, metastasis and death occurred quickly in the most aggressive bad cancers.
But after successful surgery for less aggressive cancer, they repeatedly found that disseminated cancer cells were not just dormant but were eliminated, apparently by the refocused immune response. It was clear that the immune response was essential because, once the front-line attackers called cytotoxic T cells cleared, the cancer spread more easily.
The mice were even able to fight against three subsequent injections of 100,000 cancer cells in the tail. They labeled the tumor cells that they injected, then watched them travel, like cells from the primary tumor, to the lungs, and then continued to watch the immune system eradicate them within a few days. "It's a very efficient system," says Korkaya.
The positive results occurred several weeks after the removal of the primary bad tumor, suggesting that the investigators write that the immune system remembered the attacker. In fact, six months later, the immune memory was still intact.
Conversely, when part of the primary tumor was left behind, the immune system seemed to support the tumor, which was growing and growing faster than the original mbad, disseminated cancer cells were better able to Install in other parts of the body and in the environment. the mice died soon. Scientists have observed four to ten times more myeloid-derived suppressor cells – which, as their name suggests, may suppress the immune response, particularly cytotoxic T cells – have shifted to areas where distant tumor cells were present, while useful cytotoxic T cell levels decreased. .
Furthermore, when they incorporated myeloid-derived suppressor cells from the most aggressive cancer to the less aggressive bad cancer, the mouse was no longer able to get rid of subsequent injections of cancer cells into the tail and developed a metastasis in the lungs in two weeks.
According to Korkaya, when the operation is successful, the act of cutting induces more inflammation that strengthens the immune attack against cancer. But when the tumor is left on the primary site, there is a kind of interaction that makes the immune system a friend of the tumor. He has evidence that a small molecule circulating in the blood, called granulocyte colony stimulating factor, is a culprit here, and that when it increases, it suppresses the immune response via the recruitment of these cells. suppressive agents derived from myeloid In fact, animal models of metastatic bad cancer have much higher levels of granulocyte colony stimulating factor, he says.
They are now taking blood from bad cancer patients to examine, among other things, the levels of this small molecule. He suspects that they will find that patients who do not do so have higher levels than animal models. "We want to see if there is a connection," says Korkaya.
Although there is good evidence that solid tumors send disseminated tumor cells early and continuously, it is an inefficient process with probably 90% of cells dying in transit or at the same time. Arrival, said Korkaya.
It can take up to a decade for the surviving disseminated tumor cells to develop a secondary tumor in places such as bone marrow, lungs or liver. Even after surgery, chemotherapy and / or immunotherapy, and after a patient is considered cured, a few isolated cells in these distant locations can cause a tumor.
The Korkaya team reported two years ago in Nature Communications that aggressive bad cancer recruits and uses myeloid-derived suppressive cells to allow metastasis, first by helping cancer cells to become more stem-cell-like, allowing them to migrate more The tumor secretes small signaling molecules called cytokines to obtain and maintain support for myeloid-derived suppressor cells.
Source:
https://www.augusta.edu/mcg/
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