Cancer Research

a cancer microenviroment model

Reveals spatial heterogeneity of the tumor microenvironment

Stereo-seq provides powerful tools to investigate tumor architecture and cellular diversity within the tumor microenvironment. By preserving spatial information, it allows researchers to identify distinct cell populations and their spatial relationships.

This approach supports the study of tumor progression, immune cell infiltration, and interactions between cancer and stromal cells. Furthermore, Stereo-seq aids in biomarker discovery and therapeutic target identification for precision oncology.
8
Published Papers
7+
Cancer & Disease Types

Overview

Stereo-seq empowers cancer researchers with unmatched spatial context — capturing the full complexity of tumor ecosystems while preserving the native tissue architecture that conventional methods destroy. From immune niche mapping to stromal ecosystem reconstruction, Stereo-seq reveals biology that no other approach can access.

By combining whole-transcriptome sensitivity with nanoscale resolution across large tissue sections, Stereo-seq enables simultaneous profiling of tumor cores, invasive margins, stromal boundaries, and immune infiltration zones within a single experiment.

Whole-tissue tumor ecosystem profiling in a single experiment
Near single-cell resolution across large intact tissue sections
Spatial reconstruction of tumor–stroma–immune interfaces
Identification of novel therapeutic targets and resistance mechanisms

Why Spatial Biology?

Conventional dissociated sequencing destroys the architectural context that defines tumor biology. Immune niches, stromal boundaries, metastatic gradients, and cell–cell signaling programs are only visible when tissue spatial organization is preserved. Stereo-seq captures what other methods cannot.

Research Themes Covered
Immune Architecture & Immunotherapy
Tumor Evolution, Metastasis & Resistance
Translational Biology & Beyond Oncology

Research Themes

Publications span three interconnected research areas, collectively advancing spatial tumor biology from discovery to clinical translation.

01 — Immune
Immune Architecture & Immunotherapy
Stereo-seq excels at spatial immunology — revealing immune niches that determine immunotherapy response, TLS maturation, and vascular immune portals.
02 — Evolution
Tumor Evolution, Metastasis & Resistance
Reveals spatially organized resistance mechanisms and metastatic biology that cannot be reconstructed from dissociated sequencing.
03 — Translational
Translational Biology & Beyond Oncology
Enables clinically actionable spatial biomarker discovery in acute injury and transplant medicine — expanding spatial biology beyond cancer.

Featured Publications

8 peer-reviewed papers powered by Stereo-seq, published in top-tier journals including Cancer CellNature Genetics, and Cancer Discovery.

All (8)
Immune Architecture
Tumor Evolution
Translational
Cancer Cell
Spatial transcriptomics reveals tryptophan metabolism restricting maturation of intratumoral tertiary lymphoid structures
Tang et al. · Sun Yat-sen University · 2025
Liver (HCC)
Biological Problem
HCC — ~800K deaths/year worldwide
TLS maturation states couldn't be spatially distinguished with conventional methods
Dissociated sequencing destroys TLS topology and immune gradients irretrievably
Stereo-seq Advantage
Whole-tissue mapping of all 937 TLS structures at nanoscale resolution
Reconstructed TLS maturation trajectories in situ (immature → maturing → mature)
Localized tryptophan-metabolic regions surrounding dysfunctional TLSs
Key Discoveries
TDO2-driven metabolism suppresses TLS maturation and germinal-center formation
TDO2 inhibition + anti-PD1 showed enhanced antitumor efficacy
TLS signatures correlated with improved anti-PD1 response
💡 Stereo-seq spatially resolved immune niches that directly control immunotherapy-relevant TLS maturation states.
View publication ↗DOI: 10.1016/j.ccell.2025.03.011
Cancer Discovery
Spatially Resolved Tumor Ecosystems and Cell States in Gastric Adenocarcinoma Progression and Evolution
Ma et al. · Duke-NUS / National University of Singapore · 2025
Gastric Adenocarcinoma
Biological Problem
Gastric cancer — 5th leading cause of cancer death globally
Spatial distribution of drug-resistant subclones was unknown
Geographic distribution of G1 vs G2 ecosystems not mappable without spatial context
Stereo-seq Advantage
Whole-tumor spatial continuity — preserved core–margin architecture
Near single-cell resolution resolving G1/G2 tumor ecosystems
Integrated with scRNA-seq and CNV phylogenetic reconstruction
Key Discoveries
G1 (tumor core) vs G2 (invasive margin) spatial ecosystems identified
SOX9 promotes internal diaspora evolution — validated via CRISPR
Wnt signaling enriched in G2 regions suggesting therapy resistance mechanisms
💡 Stereo-seq reconstructed gastric cancer evolution and revealed aggressive spatial tumor ecosystems invisible to conventional sequencing.
View publication ↗DOI: 10.1158/2159-8290.CD-24-0605
Cell Discovery
Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma
Cheng et al. · Fudan University · 2025
Liver (HCC)
Biological Problem
CAF subtypes drive tumor growth but spatial roles and organization were unknown
CAF-FAP vs CAF-C7 can only be distinguished by their spatial position in tissue
Stereo-seq Advantage
Simultaneously profiled tumor core, invasive margin, fibrotic capsule, and adjacent liver
Identified functional CAF-immune co-localization units across the tumor
Key Discoveries
FR+ fibrotic HCC showed better prognosis than invasive FR− stromal-rich tumors
CAF-FAP inhibitor + anti-PD1 = superior tumor regression in mouse models
New strategy: stromal depletion to rescue IO response
💡 Stereo-seq uncovered fibroblast ecosystems that spatially orchestrate immune exhaustion — directly enabling stromal therapeutic strategy.
View publication ↗DOI: 10.1038/s41421-024-00747-z
Nature Comms
Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation
Wang et al. · CAMS Cancer Hospital · 2025
Breast Cancer
Biological Problem
Leading female malignancy; IO response limited by insufficient immune infiltration
Venular immune niches are microscopic — spatial co-localization lost in dissociation
Stereo-seq Advantage
Nanoscale vascular mapping outperforming competing ST platforms
Spatially assigned CCL19/21 and ACKR1 signaling to specific vascular cell types
Profiled primary tumors and metastatic lymph nodes in preserved spatial architecture
Key Discoveries
First discovery of 'venular niche' — a spatially defined immune-entry portal in breast tumors
Vascular niche = new therapeutic target to boost immune infiltration
Most comprehensive breast tumor spatial atlas across all molecular subtypes
💡 Stereo-seq uncovered a previously invisible vascular niche controlling immune infiltration — a new target to enhance immunotherapy efficacy.
View publication ↗DOI: 10.1038/s41467-025-58511-0
Nature Genetics
Single-cell multi-omic and spatial profiling of esophageal squamous cell carcinoma reveals the immunosuppressive role of GPR116+ pericytes in cancer metastasis
Pei et al. · Guangzhou Medical University · 2025
Esophageal (ESCC)
Biological Problem
>50% ESCC patients metastatic at diagnosis; 5-year survival ~20%
No specific metastasis-driving pericyte subset had been identified in the TME
Stereo-seq Advantage
Perivascular niche resolution beyond conventional spot-based spatial platforms
Spatially resolved EGFL6–integrin β1 signaling between pericytes and tumor cells
Key Discoveries
Novel GPR116+ pericyte drives ESCC metastasis via EGFL6–integrin β1–NFκB axis
Serum EGFL6: new non-invasive biomarker distinguishing metastatic from non-metastatic ESCC
Integrin β1 antibody suppresses metastasis AND rescues immune function
💡 Stereo-seq spatially resolved metastasis-associated stromal niches — yielding a new non-invasive biomarker and therapeutic target in one discovery.
View publication ↗DOI: 10.1038/s41588-025-02341-9
Cancer Research
Spatial and Single-Cell Analyses Reveal Heterogeneity of DNAM-1 Receptor–Ligand Interactions That Instructs Intratumoral γδT-cell Activity
Wang et al. · Beijing Children's Hospital · 2025
Neuroblastoma
Biological Problem
Most common extracranial solid tumor in children; high-risk cases have very limited treatment options
CD155 suppression spatially heterogeneous across tumor regions — mechanism unknown
Stereo-seq Advantage
Resolved CD112/CD155 spatial heterogeneity beyond conventional spot-based platforms
Combined spatial transcriptomics and MSI within matched tumor regions
Key Discoveries
Spatially resolved CD155-high tumor niches driving γδT-cell exhaustion and immune escape
DNAM-1 ligand interactions identified as potential γδT-cell immunotherapy targets
Localized TIGIT/PD-1 upregulation within suppressive immune microenvironments
💡 Stereo-seq resolved immune-suppressive ligand heterogeneity — enabling precision cell therapy development for pediatric cancers.
View publication ↗DOI: 10.1158/0008-5472.CAN-24-1509
Nature Cardiovasc
Single-cell spatial transcriptomics of tertiary lymphoid organ-like structures in human atherosclerotic plaques
Lai et al. · Peking Union Medical College · 2025
Vascular / Plaque
Biological Problem
Organized adaptive immune structures in vascular plaques theorized but never confirmed in human tissue
PTLOs are spatially organized — existence can only be proven by preserving tissue structure
Stereo-seq Advantage
First-in-human PTLO confirmation via spatial resolution of lymphocyte clustering
Combined with BCR lineage mapping inside intact PTLO ecosystems
Key Discoveries
PTLOs first-ever identified in human carotid atherosclerotic plaques
PTLO presence = independent risk factor for symptomatic stroke
B cell clones shared between plaque and perivascular adipose — immune migration axis
💡 Stereo-seq uncovered organized adaptive immune ecosystems hidden inside human vascular disease — a first discovery impossible without spatial biology.
View publication ↗DOI: 10.1038/s44161-025-00639-9
Cell Reports Med
Targeting mitochondrial complex I of CD177+ neutrophils alleviates lung ischemia-reperfusion injury
Wu et al. · Shanghai Pulmonary Hospital · 2025
Lung Transplant
Biological Problem
Primary Graft Dysfunction — severe lung injury within 72h of transplant; leading cause of early post-transplant death
Cellular drivers in intact lung tissue were unknown — a critical gap preventing targeted intervention
Stereo-seq Advantage
Delineated inflamed vs unaffected lung regions — critical for mechanistic understanding
Localized NET-forming neutrophils within injured reperfusion microenvironments
Mouse model + human PGD samples profiled — directly supporting clinical application
Key Discoveries
CD177+ neutrophils identified as primary drivers of ischemia-reperfusion lung injury
Mitochondrial complex I inhibition suppresses PGD in mouse and ex vivo human models
Demonstrates Stereo-seq utility in acute inflammatory disease beyond oncology
💡 Stereo-seq identified the spatial inflammatory engine driving severe transplant lung injury — opening a new therapeutic window in acute disease.
View publication ↗DOI: 10.1016/j.xcrm.2025.102140

Why leading research centers choose Stereo-seq?

Four pillars that make Stereo-seq the definitive platform for cancer spatial biology.
🔬
Tissue-scale spatial biology
Profile intact whole-tissue ecosystems in a single experiment — tumor, stroma, vasculature, and margins simultaneously, with continuous spatial gradients across large sections.
🎯
High-resolution discovery
Resolve rare niches at near single-cell resolution. Distinguish adjacent cell states with distinct functions and localize signaling interactions to precise anatomical regions.
💊
Translational relevance
Identify biomarkers linked to prognosis and therapy response. Reveal immune suppression mechanisms, metastatic drivers, and novel therapeutic combination strategies.
🌐
Discoveries impossible otherwise
Reveal previously invisible immune and stromal micro-niches. Detect localized cell interactions missed by dissociative methods. Preserve native tissue architecture and context.