TY - JOUR TI - Characteristics and spatially-defined immune (micro)landscapes of early-stage PD-L1-positive triple-negative breast cancer AU - Carter, Jodi M. AU - Polley, Mei-Yin C. AU - Leon-Ferre, Roberto A. AU - Sinnwell, Jason AU - Thompson, Kevin J. AU - Wang, Xue AU - Ma, Yaohua AU - Zahrieh, David AU - Kachergus, Jennifer M. AU - Solanki, Malvika AU - Boughey, Judy C. AU - Liu, Minetta C. AU - Ingle, James N. AU - Kalari, Krishna R. AU - Couch, Fergus J. AU - Thompson, E. Aubrey AU - Goetz, Matthew P. T2 - Clinical Cancer Research AB - Purpose: PD-(L)1-targeted therapies have shown modest survival benefit in triple-negative breast cancer (TNBC). PD-L1+ microenvironments in TNBC are not well-characterized and may inform combinatorial immune therapies. Herein, we characterized clinicopathologic features, RNA-based immune signatures and spatially-defined protein-based immune microenvironments (TIME) in early-stage PD-L1+ and PD-L1- TNBC. Experimental Design: From a large cohort of chemotherapy-naïve TNBC, clinicopathologic features, deconvoluted RNA immune signatures, and intraepithelial and stromal TIME (Nanostring GeoMXTM) were identified in subsets of PD-L1+ and PD-L1- TNBC, as defined by FDA-approved PD-L1 companion assays. Results: 228/499 (46%) TNBC were PD-L1+ (SP142: {greater than or equal to}1% immune cells-positive). Using PD-L1 22C3, 46% had combined positive score (CPS) {greater than or equal to} 1 and 16% had CPS {greater than or equal to}10. PD-L1+ TNBC were higher grade with higher TILs (p <0.05). PD-L1 was not associated with improved survival following adjustment for TILs and other variables. RNA profiles of PD-L1+ TNBC had increased dendritic cell, macrophages and T/B cell subset features; and decreased myeloid-derived suppressor cells. PD-L1+ stromal and intraepithelial TIME were highly enriched in IDO-1, HLA-DR, CD40 and CD163 compared to PD-L1- TIME, with spatially-specific alterations in CTLA-4, STING, and fibronectin. Macrophage and antigen presentation-related proteins correlated most strongly with PD-L1 protein. Conclusions: In this early-stage TNBC cohort, nearly 50% were PD-L1+ (SP142 companion assay) while 16% were PD-L1+ with the 22C3 companion assay. PD-L1+ TNBC had specific myeloid-derived and lymphoid features. Spatially-defined PD-L1+TIME were enriched in several clinically-actionable immune proteins. These data may inform future studies on combinatorial immunotherapies for patients with PD-L1+ TNBC. DA - 2021/01/01/ PY - 2021 DO - 10.1158/1078-0432.CCR-21-0343 DP - clincancerres.aacrjournals.org J2 - Clin Cancer Res LA - en SN - 1078-0432, 1557-3265 UR - https://clincancerres.aacrjournals.org/content/early/2021/06/08/1078-0432.CCR-21-0343 Y2 - 2021/06/10/19:05:43 ER -