Myeloid-derived suppressor cells (MDSCs) are a type of immune cell that tumors recruit to help them suppress the body’s response to the invading tumor. Despite this, MDSC regulation is widely variable between cancer patients and mechanisms of MDSC-recruitment have remained largely speculative.
Now, Baylor College of Medicine scientists show tumor cells use mTOR signaling to recruit these suppressors to promote tumor growth. The findings may help in the future to more accurately diagnosis the specific type of cancer present, giving oncologists a more directed approach for therapy.
Corresponding author Xiang Zhang and his group published their recent work in the journal Nature Cell Biology.
Studying breast cancer cells, the group finds that mTOR signaling--a key pathway in cell survival--is driving the stimulation of MDSCs through the regulation of granulocyte-colony stimulating factor (G-CSF).
"There are alternative paths a tumor may take without the MDSCs, but those cancer cells that take the mTOR path of activity tend to have more MDSCs through the production of granulocyte-colony stimulating factor (G-CSF), which drives the accumulation of MDSCs," said Zhang.
They validated their findings in primary breast cancer cells and patient-derived xenografts. Referring to the increasing demands of targeted medicine in the clinic, Zhang said in a release, “People talk about the specific mutations one patient's tumor has that are not in another patient's tumor. The same type of tumors having different mutations may warrant different treatments; that is personalized medicine.
“We are trying to come from a different angle. We are trying to enrich this concept by saying that not only tumor-intrinsic characteristics are different from patient to patient, but, related to that, there is also diversity in terms of the immune components. Different tumors may evolve via different characteristics of the tumor and the immune response."
There are other types of immune cells that may promote--or resist--tumor growth but this work is unique in that it looks at the non-classical role of aberrant mTOR signaling in the host immune system.
MDSCSs are also important in suppressing the immune system when it comes to chronic inflammation. The authors admit it is therefore important to consider dangerous side-effects, such as autoimmune disease, of targeting MDSCs directly and places emphasis on the need to characterize tumor-specific MDSCs.
Image of cancer cells from human connective tissue courtesy of Dr. Cecil Fox/National Cancer Institute.