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-naive TNBC, clinicopathologic features, deconvoluted RNA immune signatures, and intraepithelial and stromal TIME (Nanostring GeoMX(TM)) 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.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
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