The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling

Journal of Translational Medicine

Briana M. Hudson¹  Ilana Schlam²  Krysta Chaldekas³  Emily Maisonet³  Brent T. Harris³  Sandra M. Swain⁴  Tyler D. Hether⁵  Sarah E. Church⁵  Andrew M. White⁵ 

[1] Department of Hematology and Oncology, Tufts Medical Center, 800 Washington St, 245, 02111, Boston, MA, USA;Department of Hematology-Oncology, MedStar Washington Hospital Center, Washington, DC, USA;Department of Hematology and Oncology, Tufts Medical Center, 800 Washington St, 245, 02111, Boston, MA, USA;MedStar Georgetown University Hospital, 4000 Reservoir road NW, 120 Building D, 20057, Washington, DC, USA;Lombardi Comprehensive Cancer Center, Washington, DC, USA;MedStar Georgetown University Hospital, 4000 Reservoir road NW, 120 Building D, 20057, Washington, DC, USA;Lombardi Comprehensive Cancer Center, Washington, DC, USA;MedStar Health, Washington, DC, USA;NanoString Technologies Inc., Seattle, WA, USA;

关键词: Breast cancer;    HER2 positive;    Tumor microenvironment;    Digital spatial profiling;    Gene expression profiling;   

DOI  :  10.1186/s12967-021-03113-9

来源: Springer

【 摘 要 】

BackgroundThe characterization of the immune component of the tumor microenvironment (TME) of human epidermal growth factor receptor 2 positive (HER2+) breast cancer has been limited. Molecular and spatial characterization of HER2+ TME of primary, recurrent, and metastatic breast tumors has the potential to identify immune mediated mechanisms and biomarker targets that could be used to guide selection of therapies.MethodsWe examined 15 specimens from eight patients with HER2+ breast cancer: 10 primary breast tumors (PBT), two soft tissue, one lung, and two brain metastases (BM). Using molecular profiling by bulk gene expression TME signatures, including the Tumor Inflammation Signature (TIS) and PAM50 subtyping, as well as spatial characterization of immune hot, warm, and cold regions in the stroma and tumor epithelium using 64 protein targets on the GeoMx Digital Spatial Profiler.ResultsPBT had higher infiltration of immune cells relative to metastatic sites and higher protein and gene expression of immune activation markers when compared to metastatic sites. TIS scores were lower in metastases, particularly in BM. BM also had less immune infiltration overall, but in the stromal compartment with the highest density of immune infiltration had similar levels of T cells that were less activated than PBT stromal regions suggesting immune exclusion in the tumor epithelium.ConclusionsOur findings show stromal and tumor localized immune cells in the TME are more active in primary versus metastatic disease. This suggests patients with early HER2+ breast cancer could have more benefit from immune-targeting therapies than patients with advanced disease.

【 授权许可】

CC BY