Spatial Mapping of the Lung Cancer Ecosystem Reveals Distinct Patterns of Intratumoral and Internodular Heterogeneity
- 1Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
Abstract
The spatial organization of malignant and non-malignant cells within the tumor microenvironment (TME) critically influences tumor evolution and therapeutic response. However, the architecture of micro-niches remains incompletely understood. Leveraging Xenium-based spatial transcriptomics, we comprehensively mapped the spatial ecosystem of an orthotopic murine lung cancer model, identifying distinct spatial domains that form unique, organized cellular neighborhoods. These domains cluster into three major communities: (1) non-tumoral regions that recapitulate canonical normal lung structures; (2) a heterogeneous peri-tumoral region composed of spatial domains characterized by mesenchymal remodeling, active immune checkpoint signaling, and immunosuppressive myeloid populations; and (3) intra-tumoral regions that reveal marked tumor nodule heterogeneity, with unique tumor-specific domains exhibiting hallmark cancer pathways. Furthermore, our analytic approach was applicable to human lung cancer tissue. Notably, spatial domain analysis allowed us to resolve tumor nodules into multiple biologically distinct subtypes, defined by domain composition, hallmark cancer programs, and intercellular communication patterns within the TME.
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BibTeX
@misc{baek2026spatial,
title = {{Spatial Mapping of the Lung Cancer Ecosystem Reveals Distinct Patterns of Intratumoral and Internodular Heterogeneity}},
author = {B.-S. Baek and K.-H. Kim and S.-j. Kim and J. D. Eccles and M. Kim and S. You and C. Ascoli and G. Y. Park},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.748358},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.748358v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Spatial Mapping of the Lung Cancer Ecosystem Reveals Distinct Patterns of Intratumoral and Internodular Heterogeneity
AU - B.-S. Baek
AU - K.-H. Kim
AU - S.-j. Kim
AU - J. D. Eccles
AU - M. Kim
AU - S. You
AU - C. Ascoli
AU - G. Y. Park
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.748358
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.748358v1
AB - The spatial organization of malignant and non-malignant cells within the tumor microenvironment (TME) critically influences tumor evolution and therapeutic response. However, the architecture of micro-niches remains incompletely understood. Leveraging Xenium-based spatial transcriptomics, we comprehensively mapped the spatial ecosystem of an orthotopic murine lung cancer model, identifying distinct spatial domains that form unique, organized cellular neighborhoods. These domains cluster into three major communities: (1) non-tumoral regions that recapitulate canonical normal lung structures; (2) a heterogeneous peri-tumoral region composed of spatial domains characterized by mesenchymal remodeling, active immune checkpoint signaling, and immunosuppressive myeloid populations; and (3) intra-tumoral regions that reveal marked tumor nodule heterogeneity, with unique tumor-specific domains exhibiting hallmark cancer pathways. Furthermore, our analytic approach was applicable to human lung cancer tissue. Notably, spatial domain analysis allowed us to resolve tumor nodules into multiple biologically distinct subtypes, defined by domain composition, hallmark cancer programs, and intercellular communication patterns within the TME.
ER -