Details

Autor(en) / Beteiligte

• Carter, Jodi M
• Polley, Mei-Yin C
• Leon-Ferre, Roberto A
• Sinnwell, Jason
• Thompson, Kevin J
• Wang, Xue
• Ma, Yaohua
• Zahrieh, David
• Kachergus, Jennifer M
• Solanki, Malvika
• Boughey, Judy C
• Liu, Minetta C
• Ingle, James N
• Kalari, Krishna R
• Couch, Fergus J
• Thompson, E Aubrey
• Goetz, Matthew P

Titel

Characteristics and Spatially Defined Immune (micro)landscapes of Early-stage PD-L1-positive Triple-negative Breast Cancer

Ist Teil von

• Clinical cancer research, 2021-10, Vol.27 (20), p.5628-5637

Ort / Verlag

United States

Erscheinungsjahr

2021

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Programmed death ligand 1 [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 tumor-immune microenvironments (TIME) in early-stage PD-L1 and PD-L1 TNBC. From a large cohort of chemotherapy-naïve TNBC, clinicopathologic features, deconvoluted RNA immune signatures, and intraepithelial and stromal TIME (Nanostring GeoMX) were identified in subsets of PD-L1 and PD-L1 TNBC, as defined by FDA-approved PD-L1 companion assays. 228 of 499 (46%) TNBC were PD-L1 (SP142: ≥1% immune cells-positive). Using PD-L1 22C3, 46% had combined positive score (CPS) ≥ 1 and 16% had CPS ≥10. PD-L1 TNBC were higher grade with higher tumor-infiltrating lymphocytes (TIL; < 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, macrophage, and T/B cell subset features; and decreased myeloid-derived suppressor cells. PD-L1+ stromal and intraepithelial TIMEs were highly enriched in IDO-1, HLA-DR, CD40, and CD163 compared with PD-L1-TIME, with spatially specific alterations in CTLA-4, Stimulator of Interferon Genes (STING), and fibronectin. Macrophage- and antigen presentation-related proteins correlated most strongly with PD-L1 protein. 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. .