A study, published in the journal Cell Stem Cell, explains how breast cancers evade the defenses of the immune system to continue developing. The research, conducted in animal models, shows that breast cancers send molecular signals to the bone marrow, the cradle of immune cells, and that these signals alter the bone marrow’s natural environment in such a way that it suppresses the tumor-fighting response. .
Interestingly, these changes persist long after the tumor is removed.
The researchers, coordinated from the Baylor College of Medicine (USA) also identified ways to accelerate the restoration of normal conditions in the bone marrow after the removal of the tumor, accelerating the recovery of the immune system.
The findings warrant further research that could lead to better treatments for patients.
“Research has shown that breast cancer can have a significant impact on the body even before it metastasizes or spreads to other organs. For example, tumors can remotely alter the ecosystem of the bone marrow, triggering an immune response that does not attack the tumor, but favors its growth,” Xiang H.-F explains. Zhang and William T. Butler, study authors. To understand how this happens, we characterize the organization of the bone marrow in animal models of breast cancer before the tumor had metastasized.”
The team found that even small tumors can profoundly affect the body, triggering multiple changes in the bone marrow.
“Breast tumors promote the overproduction of bone marrow cells called osteoprogenitoraswhich will later contribute to new bone formation,” explains first author Xiaoxin Hao.
In addition, other cells, the progenitor cells that give rise to immune cells, also grow in number. More importantly, these progenitors also change their typical location within the bone marrow, relocating close to osteoprogenitor cells and establishing new cell-to-cell communication with these cells, particularly with a subset called granulocyte-monocyte progenitors (GMPs). ).
“We think this osteoprogenitor-GMP communication is key, because GMPs give rise to neutrophils and monocytes, immune cells that have long been known to accumulate in some breast cancer tumors in patients and mouse models of breast cancer and they help promote tumor growth by suppressing the anti-tumor immune response,” Hao said.
The researchers were surprised to find that after removing the tumor, which they considered the source of the problem, the bone marrow disorder did not recover immediately.
“We observed this in animal models,” Hao said. “In some patients, we have seen that even more than 40 weeks after removing the tumor, there are still increased numbers of neutrophils in their blood, which is clinically relevant.”
In some cases, removal of the tumor is followed by immunotherapy, the success of which depends on an intact immune system. “Our findings suggest that, at least in some patients, the immune system remains compromised after tumor removal, which likely reduces the beneficial effects of immunotherapy,” Zhang says.
Our findings suggest a new treatment modality that is very different from current strategies.
Furthermore, the findings have implications for metastasis. Metastasis can arise years or even decades after the surgical removal of the tumor, seeded by residual cancer cells left behind after the intervention. “A persistent immunosuppressive effect after the operation can create a favorable environment for residual cancer cells to proliferate and metastasize,” Hao explains.
The researchers also identified the MMP-13 protein as an essential mediator of crosstalk between osteoprogenitor cells and MMPs. “We show that if we knock out or inhibit MMP-13, we can speed up the recovery of the immune system and restore the efficacy of immunotherapies,” Hao said.
“Our findings suggest a new treatment modality that is very different from current strategies. It doesn’t target cancer cells, it doesn’t target immune T cells that attack cancer cells, it targets the whole body. It’s about removing a kind of shadow cast over the entire immune system,” Zhang explains. “This is just the beginning of a series of studies about how tumors alter the entire organism. Our findings support the continuation of our research on this path, and we hope that it will lead to the identification of improved treatments for cancer patients.”
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