IU researchers identify how breast cancer cells avoid immune attacks

Researchers at the Melvin and Bren Simon Comprehensive Cancer Center have identified how breast cancer cells hide from immune cells to survive. The finding could lead to better immunotherapy treatment for patients.

Xinna Zhang, PhD, and colleagues found that when breast cancer cells contain a higher level of a protein called MAL2, the cancer cells can evade immune attacks and continue to grow. The findings are published this month in The Journal of Clinical Research and can be seen on the cover of the magazine.

The lead author of the study, Zhang is a member of the IU Simon Comprehensive Cancer Center and assistant professor of medical and molecular genetics at the IU School of Medicine.

Considered the future of cancer treatment, immunotherapy uses the body’s immune system to target and destroy cancer cells. Understanding how cancer cells evade immune attacks could offer patients new ways to develop immunotherapy, explained Xiongbin Lu, PhD, Vera Bradley Foundation Professor in Breast Cancer Innovation and cancer center research.

“Conventional cancer immunotherapy has remarkable results in some patients, but more than 70% of breast cancer patients do not respond to cancer immunotherapy,” Lu said. “One of the biggest reasons tumors are developing equipment to avoid the immune attacks.”

The collaborative research team aimed to answer key questions: How do breast cancer cells develop this immune clearance, and could they target that activity leading to better immunotherapies ?

Zhang and Lu, members of the Vera Bradley Foundation Center for Breast Cancer Research, turned to biochemical data researcher Chi Zhang, PhD, assistant professor of medical and molecular genetics at the IU School of Medicine. Chi Zhang developed a computational method to analyze data sets from more than 1,000 breast cancer patients through the Atlas Genome. That analysis brought researchers to MAL2; it showed that higher levels of MAL2 in breast cancer, and especially in triple-negative breast cancer (TNBC), were associated with worse patient survival.

Dr. Chi Zhang used his advanced computational tool to build a bridge that connects cancer genetics and cancer genomics with clinical outcome. We can study the molecular properties of thousands of breast tumor samples to identify potential targets for cancer immunotherapy. From that data, MAL2 was the highest gene we wanted to study. “

Xiongbin Lu, PhD, Vera Bradley Foundation Professor of Breast Cancer Innovation and Cancer Center Researcher

Xinna Zhang took that data to her lab to determine the cause of MAL2 in the cells, how it affects breast cancer cell growth and how it interacts with immune cells. Using breast cancer strain samples from IU patients, cell models and animal models, she found that breast cancer cells express more MAL2 than normal cells. She also found that high levels of MAL2 significantly contributed to tumor growth, while inhibiting the protein almost completely inhibited tumor growth.

In Lu’s laboratory, he used a three-dimensional, patient-centered model called organoid to better understand how MAL2 reduction could improve patient outcomes.

“Tumor cells can prevent immune attacks; with less MAL2, the cancer cells can recognize and kill the immune system,” Lu said. “MAL2 is a novel target. By highlighting its role in cancer cells and cancer immunology, we now know its potential as a target of cancer vaccines.”

Researchers are now exploring ways to use these products to develop and promote breast cancer treatments.

Lu is co-leading a cancer immunotherapy program for triple-negative breast cancer as part of Indiana University’s Precision Health Initiative. Both Xinna Zhang and Chi Zhang are also involved in the campaign to develop new breast cancer immunotherapy. The Precision Health Initiative, the first recipient of funding from Indiana University’s Major Challenge Program, promotes the prevention, treatment and health outcomes of human diseases through a more in-depth study of the genetic, developmental, behavioral and environmental factors that shape a person’s health. . .