New discovery may drive the development of better, more effective immunotherapies for the treatment of breast cancer

Irvine, CA. – February 21, 2020 

New cancer immunotherapy approaches are revolutionizing treatment options for breast cancer patients.  However, many lead to insufficient immune responses rendering the therapies incapable of completely eradicating tumors.

In a new study, published today in Science Immunology, University of California, Irvine researchers determined the molecular features of certain cells associated with breast cancer, which may open up new avenues into improving cancer immunotherapy. 

“One reason for the poor response to immunotherapy can be the presence of breast cancer-associated myeloid-derived suppressor cells (MDSCs), which have immunosuppressive capacity in the tumor microenvironment,” said Kai Kessenbrock, PhD, assistant professor of biological chemistry at the UCI School of Medicine.  “Until now, these cells have remained poorly characterized. In particular, it was difficult to determine the difference between MDSCs and normal myeloid cells in healthy individuals. Because of the difficulty in distinguishing these diverse myeloid cells, our ability to detect and therapeutically target MDSCs during cancer was limited.”

Lead researcher, UCI’s Hamad Alshetaiwi, and his colleagues in the Kessenbrock lab teamed up with members of UCI School of Biological Sciences professor Craig Walsh’s lab and, using cutting edge single cell gene expression analyses, determined the molecular features of MDSCs.  They did this by sequencing about 15,000 individual cells, detecting thousands of genes expressed in each one. These complex datasets were analyzed using a diverse pipeline of computational analyses tools, which revealed that MDSCs emerge through an unusual path of neutrophil maturation that confers them an immunosuppressive cell state.

“We established a MDSC-specific gene signature and identified CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers.  With this new information, we can increase our ability to detect and target MDSCs during cancer and potentially improve cancer immunotherapies by directly interfering with these cells in breast cancer patients,” said Alshetaiwi.

Breast cancer is one of the most prevalent types of cancer with more than 260,000 new cases and more than 40,000 deaths in 2018 in the United States. 

This study was supported in part by funding from the National Institutes of Health/National Cancer Institute and the American Cancer Society.

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Each year, the UCI School of Medicine educates more than 400 medical students and nearly 150 PhD and MS students. More than 700 residents and fellows are trained at the UCI Medical Center and affiliated institutions. Multiple MD, PhD and MS degrees are offered. Students are encouraged to pursue an expansive range of interests and options. For medical students, there are numerous concurrent dual degree programs, including an MD/MBA, MD/MPH, or an MD/MS degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Program in Medical Education for Leadership Education to Advance Diversity-African, Black and Caribbean (PRIME LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit medschool.uci.edu.