Cell-related discovery may improve immunotherapy for breast cancer

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Caption: By carrying out scRNAseq in a model of breast cancer, a UCI-led research team has defined gene signatures that distinguish MDSCs from other myeloid and granulocytic cells. Above is an artistic rendering of single cell transcriptomics analysis showing clusters of diverse immune cell populations from the spleens of tumor-bearing mice.

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 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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Cell-related discovery may improve immunotherapy for breast cancer.  Appl Rad Oncol. 

By News Release| March 11, 2020

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