Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers.

Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers.
J Clin Invest. 2019 Feb 12;:
Authors: Gruosso T, Gigoux M, Manem VSK, Bertos N, Zuo D, Perlitch I, Saleh SMI, Zhao H, Souleimanova M, Johnson RM, Monette A, Ramos VM, Hallett MT, Stagg J, Lapointe R, Omeroglu A, Meterissian S, Buisseret L, Van den Eynden G, Salgado R, Guiot MC, Haibe-Kains B, Park M
Abstract
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, a type I interferon signature, elevated expression of multiple immune inhibitory molecules, including IDO, PD-L1, and good outcome. An "immune-cold" microenvironment with absence of tumoral CD8+ T cells was defined by elevated expression of the immunosuppressive marker B7-H4, signatures of fibrotic stroma and poor outcome. 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. Metasignatur...

Source: Clinical Breast Cancer - February 12, 2019 Category: Cancer & Oncology Authors: Gruosso T, Gigoux M, Manem VSK, Bertos N, Zuo D, Perlitch I, Saleh SMI, Zhao H, Souleimanova M, Johnson RM, Monette A, Ramos VM, Hallett MT, Stagg J, Lapointe R, Omeroglu A, Meterissian S, Buisseret L, Van den Eynden G, Salgado R, Guiot MC, Haibe-Kains B, Tags: J Clin Invest Source Type: research