OpenTME: An Open Dataset of AI-powered H&E Tumor Microenvironment Profiles from TCGA

Hematoxylin and eosin (H&E) staining is the cornerstone of histopathology, yet scalable, quantitative analysis of H&E whole-slide images (WSIs) remains a central challenge in computational pathology. We present Atlas H&E-TME, an AI-based system built on the Atlas family of pathology foundation models that predicts tissue quality, tissue region, and cell type labels across multiple cancer types, yielding over 4,500 quantitative readouts per slide at cell-level resolution. A key challenge to validating such systems is overcoming morphological ambiguity inherent to H&E-only ground truth and the limited scalability of more informed references drawing on modalities such as immunohistochemistry (IHC). We address this with a dual validation framework combining biologically grounded depth with technical and morphological breadth. For depth, we propose an IHC-informed multi-pathologist consensus protocol that substantially improves inter-rater agreement over conventional H&E-only annotation. This yields a molecularly grounded reference against which we compare Atlas H&E-TME and pathologists working from H&E alone. For breadth, we benchmark Atlas H&E-TME on over 200,000 high-confidence H&E-only pathologist annotations across 1,500+ cases spanning eight cancer types and their most common metastatic sites, with subtypes covering >90% of clinical cases per cancer type, drawn from 25+ sources and 8+ scanner models. Benchmarked against the IHC-informed consensus, Atlas H&E-TME matches or exceeds pathologist H&E-only performance and generalizes consistently and robustly across this broad morphological and technical scope. In doing so, Atlas H&E-TME turns the H&E slide -- the most ubiquitous data in pathology -- into a scalable, quantitative window into the tumor and its microenvironment, laying a foundation for the next generation of tissue-based biomarkers in translational and clinical research.

Characterising the TME from routine H&E-stained histology images requires simultaneous cell segmentation, biological feature extraction, and interpretable clinical reporting. We present SegTME-UNI2, a unified framework addressing all three requirements end-to-end: a segmentation backbone that converts raw H&E patches into per-nucleus class labels, a structured feature-extraction pipeline that turns those labels into quantitative TME descriptors, and a language-model narrative generator that turns those descriptors into clinician-readable text. At its core is UNI2-UperHoVer, a dual-head multiscale segmentation model that pairs UNI2 with two parallel UperNet decoders: one for six-class semantic segmentation and one for HV gradient regression enabling watershed-based nuclear instance separation. It is trained via a three-stage progressive pseudo-label curriculum, scaling from PanNuke (Stage 1, 0.25um/pixel) to TCGA-UT Scale-0 (Stage 2, 0.5um/pixel) and full 1.6M-patch, six-scale TCGA-UT (Stage 3, 0.5 to 1.0um/pixel). TCGA-UT's coarser, broader per-patch context than PanNuke's also permits a larger tile stride during whole-slide inference. This pipeline computes 22 per-patch compositional, morphological, spatial-entropy, and intercellular-distance metrics and translates them into six categorical phenotype labels and a standardised biological-token vocabulary, fine-tuned via NVIDIA BioNeMo that converts into clinically grounded narratives whose individual claims can be spot-checked directly against the underlying features. Qualitative validation on IGNITE NSCLC tiles shows the pipeline produces biologically coherent phenotype classifications and narratives despite inter-institutional stain variability and imperfect segmentation. The pseudo-labelled TCGA-UT dataset and UNI2-UperHoVer checkpoints are publicly released to support large-scale TME profiling and spatial biology research.

We present HistoAtlas, a pan-cancer computational atlas that extracts 38 interpretable histomic features from 6,745 diagnostic H&E slides across 21 TCGA cancer types and systematically links every feature to survival, gene expression, somatic mutations, and immune subtypes. All associations are covariate-adjusted, multiple-testing corrected, and classified into evidence-strength tiers. The atlas recovers known biology, from immune infiltration and prognosis to proliferation and kinase signaling, while uncovering compartment-specific immune signals and morphological subtypes with divergent outcomes. Every result is spatially traceable to tissue compartments and individual cells, statistically calibrated, and openly queryable. HistoAtlas enables systematic, large-scale biomarker discovery from routine H&E without specialized staining or sequencing. Data and an interactive web atlas are freely available at https://histoatlas.com .