Distinct spatial immune microlandscapes are independently associated with outcomes in triple-negative breast cancer.
Jodi M CarterSaranya ChumsriDouglas A HinerfeldYaohua MaXue WangDavid ZahriehDavid W HillmanKathleen S TennerJennifer M KachergusHeather Ann BrauerSarah E WarrenDavid HendersonJi ShiYi LiuHeikki JoensuuHenrik LindmanRoberto A Leon-FerreJudy C BougheyMinetta C LiuJames N IngleKrishna R KalariFergus J CouchKeith L KnutsonMatthew P GoetzEdith A PerezE Aubrey ThompsonPublished in: Nature communications (2023)
The utility of spatial immunobiomarker quantitation in prognostication and therapeutic prediction is actively being investigated in triple-negative breast cancer (TNBC). Here, with high-plex quantitative digital spatial profiling, we map and quantitate intraepithelial and adjacent stromal tumor immune protein microenvironments in systemic treatment-naïve (female only) TNBC to assess the spatial context in immunobiomarker-based prediction of outcome. Immune protein profiles of CD45-rich and CD68-rich stromal microenvironments differ significantly. While they typically mirror adjacent, intraepithelial microenvironments, this is not uniformly true. In two TNBC cohorts, intraepithelial CD40 or HLA-DR enrichment associates with better outcomes, independently of stromal immune protein profiles or stromal TILs and other established prognostic variables. In contrast, intraepithelial or stromal microenvironment enrichment with IDO1 associates with improved survival irrespective of its spatial location. Antigen-presenting and T-cell activation states are inferred from eigenprotein scores. Such scores within the intraepithelial compartment interact with PD-L1 and IDO1 in ways that suggest prognostic and/or therapeutic potential. This characterization of the intrinsic spatial immunobiology of treatment-naïve TNBC highlights the importance of spatial microenvironments for biomarker quantitation to resolve intrinsic prognostic and predictive immune features and ultimately inform therapeutic strategies for clinically actionable immune biomarkers.
Keyphrases
- high grade
- bone marrow
- magnetic resonance
- ms ms
- amino acid
- binding protein
- type diabetes
- metabolic syndrome
- adipose tissue
- liquid chromatography tandem mass spectrometry
- combination therapy
- high performance liquid chromatography
- solid phase extraction
- computed tomography
- high resolution
- tandem mass spectrometry
- liquid chromatography
- glycemic control