Palakurthi, BhavanaFross, Shaneann R.Guldner, Ian H.Aleksandrovic, EmilijaLiu, XiyuMartino, Anna K.Wang, QingfeiNeff, Ryan A.Golomb, Samantha M.Lewis, CherylPeng, YanHowe, Erin N.Zhang, Siyuan2023-12-152023-12-152023-04-13Palakurthi B, Fross SR, Guldner IH, et al. Targeting CXCL16 and STAT1 augments immune checkpoint blockade therapy in triple-negative breast cancer. Nat Commun. 2023;14(1):2109. Published 2023 Apr 13. doi:10.1038/s41467-023-37727-yhttps://hdl.handle.net/1805/37361Chemotherapy 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.en-USAttribution 4.0 InternationalCancer immunotherapyMonocytesMacrophagesRNA sequencingImmunosurveillanceArticle