Author:
Kim Albert E.,Lou Kevin W.,Giobbie-Hurder Anita,Chang Ken,Gidwani Mishka,Hoebel Katharina,Patel Jay B.,Cleveland Mason C.,Singh Praveer,Bridge Christopher P.,Ahmed Syed Rakin,Bearce Benjamin A.,Liu William,Fuster-Garcia Elies,Lee Eudocia Q.,Lin Nancy U.,Overmoyer Beth,Wen Patrick Y.,Nayak Lakshmi,Cohen Justine V.,Dietrich Jorg,Eichler April,Heist Rebecca,Krop Ian,Lawrence Donald,Ligibel Jennifer,Tolaney Sara,Mayer Erica,Winer Eric,Perrino Carmen M.,Summers Elizabeth J.,Mahar Maura,Oh Kevin,Shih Helen A.,Cahill Daniel P.,Rosen Bruce R.,Yen Yi-Fen,Kalpathy-Cramer Jayashree,Martinez-Lage Maria,Sullivan Ryan J.,Brastianos Priscilla K.,Emblem Kyrre E.,Gerstner Elizabeth R.
Abstract
AbstractStructurally and functionally aberrant vasculature is a hallmark of tumor angiogenesis and treatment resistance. Given the synergistic link between aberrant tumor vasculature and immunosuppression, we analyzed perfusion MRI for 44 patients with brain metastases (BM) undergoing treatment with pembrolizumab. To date, vascular-immune communication, or the relationship between immune checkpoint inhibitor (ICI) efficacy and vascular architecture, has not been well-characterized in human imaging studies. We found that ICI-responsive BM possessed a structurally balanced vascular makeup, which was linked to improved vascular efficiency and an immune-stimulatory microenvironment. In contrast, ICI-resistant BM were characterized by a lack of immune cell infiltration and a highly aberrant vasculature dominated by large-caliber vessels. Peri-tumor region analysis revealed early functional changes predictive of ICI resistance before radiographic evidence on conventional MRI. This study was one of the largest functional imaging studies for BM and establishes a foundation for functional studies that illuminate the mechanisms linking patterns of vascular architecture with immunosuppression, as targeting these aspects of cancer biology may serve as the basis for future combination treatments.
Publisher
Cold Spring Harbor Laboratory