Pan-cancer spatial characterization of key immune biomarkers in the tumor microenvironment
J Lindsay, Jennifer Altreuter, Joao V. Alessi, Jason L. Weirather, Anita Giobbie‐Hurder, Ian Dryg, Katharina Hoebel, Bijaya Sharma, Kristen D. Felt, F Stephen Hodi, Neal I. Lindeman, Lynette M. Sholl, Ethan Cerami, Jonathan A. Nowak, Mark M. Awad, Scott J. Rodig, William Lotter
Abstract
Deciphering the composition and spatial organization of the tumor immune microenvironment (TIME) is key to understanding cancer progression and treatment response. Spatial biology techniques such as multiplex immunofluorescence (mIF) offer detailed insights but are often limited to retrospective studies of individual cancer types. Here, we provide a pan-cancer spatial characterization of key biomarkers (CD8, FOXP3, PD-1, and PD-L1) using an mIF assay performed prospectively in a clinical setting on 2,019 tumors across 14 major cancer types. By integrating interpretable compositional and spatial metrics, we identify patterns of TIME variation conserved across cancer types and stages. We assess associations between these TIME spatial factors and tumor, genomic, and clinical features, with results extending prior findings and uncovering new links. To accompany the analysis, we provide a curated database of the 39.4 million spatially resolved cells. Altogether, our findings and database offer pan-cancer insights of the TIME to advance spatial biology and cancer immunology.