ArticleCancers2025
Spatial Proximity of Immune Cell Pairs to Cancer Cells in the Tumor Microenvironment as Biomarkers for Patient Stratification.
Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- SpaPheno: linking spatial transcriptomics to clinical phenotypes with interpretable machine learning.Genome medicine · 2026Article
- Deciphering immunosuppressive niches by spatial single-cell proteomics: spatial interaction networks and translational opportunities.Frontiers in immunology · 2026Review
- The chemokine network in lupus nephritis: pathogenesis, targeted therapies, and future directions.Frontiers in pharmacology · 2026Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
BACKGROUND/
objectivesThe tumor microenvironment (TME) plays a critical role in cancer progression by shaping immune responses and influencing patient outcomes. We hypothesized that the relative proximity of specific immune cell pairs to cancer cells within the TME could help predict their pro- or anti-tumor functions and reflect clinically relevant immune dynamics.
methodsWe analyzed imaging mass cytometry (IMC) data from lung adenocarcinoma (LUAD) and triple-negative breast cancer (TNBC) cohorts. For each immune cell pair, we calculated a relative distance (RD) score, which quantifies the spatial difference in proximity to cancer cells. We assessed the prognostic and predictive significance of these RD-scores by comparing them with conventional features such as cell fractions, densities, and individual cell distances. To account for variations in cell abundance, we also derived normalized RD-scores (NRD-scores).
resultsRD-scores were more strongly associated with overall patient survival than standard immunological metrics. Among all immune cell pairs, the RD-score comparing the proximity of B cells to that of intermediate monocytes showed the most significant association with improved survival. In TNBC, RD-scores also improved the distinction between responders and non-responders to immunochemotherapy and chemotherapy. Normalized RD-scores reinforced these findings by minimizing the influence of cell density and further highlighting the importance of immune cell spatial relationships.
conclusionsRD-scores offer a spatially informed biomarker that outperforms traditional metrics in predicting survival and treatment response. This approach provides a new perspective on immune cell behavior in the TME and has potential utility in guiding personalized cancer therapies and patient stratification.
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