Browsing by Author "Fross, Shaneann R."

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    Targeting CXCL16 and STAT1 augments immune checkpoint blockade therapy in triple-negative breast cancer
    (Springer Nature, 2023-04-13) Palakurthi, Bhavana; Fross, Shaneann R.; Guldner, Ian H.; Aleksandrovic, Emilija; Liu, Xiyu; Martino, Anna K.; Wang, Qingfei; Neff, Ryan A.; Golomb, Samantha M.; Lewis, Cheryl; Peng, Yan; Howe, Erin N.; Zhang, Siyuan; Biochemistry and Molecular Biology, School of Medicine
    Chemotherapy prior to immune checkpoint blockade (ICB) treatment appears to improve ICB efficacy but resistance to ICB remains a clinical challenge and is attributed to highly plastic myeloid cells associating with the tumor immune microenvironment (TIME). Here we show by CITE-seq single-cell transcriptomic and trajectory analyses that neoadjuvant low-dose metronomic chemotherapy (MCT) leads to a characteristic co-evolution of divergent myeloid cell subsets in female triple-negative breast cancer (TNBC). Specifically, we identify that the proportion of CXCL16 + myeloid cells increase and a high STAT1 regulon activity distinguishes Programmed Death Ligand 1 (PD-L1) expressing immature myeloid cells. Chemical inhibition of STAT1 signaling in MCT-primed breast cancer sensitizes TNBC to ICB treatment, which underscores the STAT1’s role in modulating TIME. In summary, we leverage single-cell analyses to dissect the cellular dynamics in the tumor microenvironment (TME) following neoadjuvant chemotherapy and provide a pre-clinical rationale for modulating STAT1 in combination with anti-PD-1 for TNBC patients.