Spatial Proximity of Immune Cell Pairs to Cancer Cells in the Tumor Microenvironment as Biomarkers for Patient Stratification

作者：Jiànróng Lǐ, Xingxin Pan, Yupei Lin, Yanding Zhao, Yanhong Liu, Yong Li, Christopher I. Amos, Chao Cheng · 发表于：Cancers · 年份：2025 · DOI：10.3390/cancers17142335 · 被引用次数：6 · 研究领域：Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

BACKGROUND/OBJECTIVES: The 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. METHODS: We 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). RESULTS: RD-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 spati...