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Stephanie Downs-Canner, MDCongratulations to Stephanie Downs-Canner, MD, Assistant Professor in the Division of Surgical Oncology and Endocrine Surgery on receiving a UNC Lineberger Development Award.

The UNC Lineberger Developmental Funding Program is intended to support the development of cancer research led by the faculty of the University of North Carolina at Chapel Hill and to stimulate new applications for extramural funding. All UNC Lineberger Comprehensive Cancer Center members, UNC-Chapel Hill faculty, and UNC system school faculty are encouraged to apply.

Dr. Downs-Canner and her co-investigator Jonathan Serody, MD, the Elizabeth Thomas Professor of Medicine, in the Division of Microbiology and Immunology in the Department of Medicine were awarded a Tier 2 stimulus award of $200,000 for their project titled, “Characterizing the Endogenous Antibody Response in Triple Negative Breast Cancer.” Their collaborators include Benjamin Vincent, MD, an Assistant Professor of Medicine, and  Laura Herring, Ph.D. Assistant Professor and Director, Michael J. Hooker Proteomics Core.

The Tier 2 Stimulus Award is intended to support innovative research initiatives aimed at obtaining sufficient data to allow new applications for extramural funding. Tier 2 may have a larger budget and/or a longer time-frame than Tier 1, and require preliminary data to support the research questions.

Scientific abstract:

Breast cancer is the leading cause of cancer-related death in women. Triple negative breast cancer (TNBC)
has the worst prognosis of all breast cancer subtypes and treatment options are limited to traditional cytotoxic
chemotherapy. Unlike other cancers, where T-cells play a critical role, recent data has shown that in TNBC, Bcells
in the tumor microenvironment (TME) are predictive of an improved outcome and may play a role in
effective immunotherapy for TNBC. Using single-cell RNA sequencing of human breast cancers, we have
identified at least 9 distinct clusters of B-cells in the TME as well as clonal restriction of B-cell receptors
(suggestive of a tumor-antigen specific immune response). The overall goal of this proposal is to understand
the activity of B cells in TNBC and use clonally restricted B-cells to identify novel antigen targets. In Aim 1, we
will use single-cell RNA sequencing of tumor-infiltrating immune cells to test our hypothesis that B-cells in
TNBC undergo clonal selection and affinity maturation in a germinal center reaction to yield clonally expanded
B-cells that are phenotypically distinct from non-clonally expanded B-cells. In Aim 2, we will clone antibodies
from the most abundant B-cell clones to discover antigens and test our hypothesis that B-cells recognize
endogenous antigens present in the TME that 1) mediate anti-tumor activity and 2) make antibodies that
recognize shared determinants present in different patients. The identification of these antibodies can be used
as potential therapeutic or diagnostic approaches for women with TNBC.