A Cascade of Immune Processes Offers Insights to Triple-Negative Breast Cancer

Researchers have discovered the process that allows immune suppressor cells to develop, suggesting a potential new way to bolster immunotherapy treatment.

11:00 AM

Author | Nicole Fawcett

Cancer is crafty. To survive and thrive, tumors find a way of thwarting our body's natural systems.

ASK ALEXA: Add the Michigan Medicine News Break to Your Flash Briefing

By looking at these systems, researchers at the University of Michigan Rogel Cancer Center have discovered that tumor cells reprogram metabolic pathways to gain control over a type of immune cell that allows cancer growth.

Myeloid-derived suppressor cells live in the tumor microenvironment and work to block cancer immunity. They also encourage a stem cell-like growth that's linked to more aggressive cancer. Patients with a lot of these suppressor cells typically have worse outcomes. Essentially, their immune system isn't strong enough to fight against the tumor.

Further, when there are a large number of myeloid-derived suppressor cells, immunotherapy treatments tend to be ineffective because the immune T-cells are suppressed.

By looking at triple-negative breast cancer cells, researchers found that the metabolic process by which cells break down glucose also regulates the expression of a specific isoform of C/EBP-beta that in turn causes more suppressor cells to develop. The immune system can't mount enough of an assault on the tumor cells, which translates to poor outcomes in triple-negative breast cancer patients.

We hope that by understanding the biology better, it may lead to new ways to help these patients.
Weiping Zou, M.D., Ph.D.

"We don't have many treatment options for triple-negative breast cancer. One of the immunological reasons may be that these tumors have a large number of myeloid suppressor cells. This could be an issue. We hope that by understanding the biology better, it may lead to new ways to help these patients," says Weiping Zou, M.D., Ph.D., the Charles B. de Nancrede Professor of Surgery, Pathology, Immunology and Biology at the University of Michigan.

Essentially, it's a cascade: The process glycolysis initiates things. It targets a molecular mechanism called LAP, a specific isoform of C/EBP-beta, which then controls expression of G-CSF and GM-CSF, small proteins made by tumor cells, which support myeloid suppressor cells and result in immunosuppression.

MORE FROM THE LAB: Subscribe to our weekly newsletter

Researchers examined this relationship in triple-negative breast cancer cell lines and in mouse models. They then looked at patient tumor samples to assess how the metabolic pathway, the number of suppressor cells and immune signatures linked with patient survival. Looking at samples from 250 triple-negative breast cancer patients, they found that when the metabolic pathway for glycolysis was enriched, so were the immune suppressor cells — and this linked with worse overall survival. In contrast, tumors with a high T-cell signature exhibited fewer of these suppressor cells and the patients had better outcomes.

The researchers will examine potential mechanisms to target this cascade. The study is published in Cell Metabolism.

Read the research papers about cancer and decision-making published by members of Cansort, the Cancer Surveillance and Outcomes Research Team.

Learn more about the University of Michigan's Cancer Genetics Program  https://www.rogelcancercenter.org/cancer-genetics.


More Articles About: Lab Report Breast cancer Cancer Research Cancer: Cancer Types
Health Lab word mark overlaying blue cells
Health Lab

This article is from the Health Lab digital publication.

Media Contact Public Relations

Department of Communication at Michigan Medicine

MichMedmedia@med.umich.edu

734-764-2220

Newsletter

Get a weekly digest of medical research and innovation, straight to your inbox.

Subscribe
Featured News & Stories lymph nodes breast cancer under microscope
Health Lab
Study finds nanomedicine targeting lymph nodes key to triple negative breast cancer treatment
In mice, nanomedicine can remodel the immune microenvironment in lymph node and tumor tissue for long-term remission and lung tumor elimination in this form of metastasized breast cancer.
older woman sitting in chair looking at window in white shirt
Health Lab
Patients with Metastatic Breast Cancer and High Mutational Burden Benefit from Pembrolizumab
Study findings support the recent FDA approval of the immunotherapy agent for patients whose cancers have high number of mutations.
Health Lab
By Cannibalizing Nearby Stromal Stem Cells, Some Breast Cancer Cells Gain Invasion Advantage
Cancer biologists and engineers collaborated on a device that could help predict the likelihood of breast cancer metastasis.
Health Lab
How a Small Implanted Device Could Help Limit Metastatic Breast Cancer
Learn about a small implanted device capable of detecting and treating metastatic breast cancer earlier and how this technology could improve survival rates.
microscope cells glioma
Health Lab
Researchers circumvent radiation resistance in subtype of brain tumors
University of Michigan Rogel Cancer Center researchers find ZMYND8 gene plays a critical role in conferring radiation resistance on brain tumors with IDH1 mutation.
tavr stroke blue cardiovascular red inside blue background
Health Lab
Hospitals without highest stroke care designation may miss them after heart procedure
Using stroke as a measure of quality after TAVR could put stroke centers at a disadvantage, the study suggests