Details

Autor(en) / Beteiligte

• Gruosso, Tina
• Gigoux, Mathieu
• Manem, Venkata Satya Kumar
• Bertos, Nicholas
• Zuo, Dongmei
• Perlitch, Irina
• Saleh, Sadiq Mehdi Ismail
• Zhao, Hong
• Souleimanova, Margarita
• Johnson, Radia Marie
• Monette, Anne
• Ramos, Valentina Muñoz
• Hallett, Michael Trevor
• Stagg, John
• Lapointe, Réjean
• Omeroglu, Atilla
• Meterissian, Sarkis
• Buisseret, Laurence
• Van den Eynden, Gert
• Salgado, Roberto
• Guiot, Marie-Christine
• Haibe-Kains, Benjamin
• Park, Morag

Titel

Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers

Ist Teil von

• The Journal of clinical investigation, 2019-04, Vol.129 (4), p.1785-1800

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Understanding the tumor immune microenvironment (TIME) promises to be key for optimal cancer therapy, especially in triple-negative breast cancer (TNBC). Integrating spatial resolution of immune cells with laser capture microdissection gene expression profiles, we defined distinct TIME stratification in TNBC, with implications for current therapies including immune checkpoint blockade. TNBCs with an immunoreactive microenvironment exhibited tumoral infiltration of granzyme B+CD8+ T cells (GzmB+CD8+ T cells), a type 1 IFN signature, and elevated expression of multiple immune inhibitory molecules including indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand 1 (PD-L1), and resulted in good outcomes. An "immune-cold" microenvironment with an absence of tumoral CD8+ T cells was defined by elevated expression of the immunosuppressive marker B7-H4, signatures of fibrotic stroma, and poor outcomes. A distinct poor-outcome immunomodulatory microenvironment, hitherto poorly characterized, exhibited stromal restriction of CD8+ T cells, stromal expression of PD-L1, and enrichment for signatures of cholesterol biosynthesis. Metasignatures defining these TIME subtypes allowed us to stratify TNBCs, predict outcomes, and identify potential therapeutic targets for TNBC.