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 spatial relationships. Conclusions: RD-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.
**背景/目的：** 肿瘤微环境通过塑造免疫反应和影响患者预后，在癌症进展中起着关键作用。我们假设，肿瘤微环境中特定免疫细胞对相对于癌细胞的相对邻近性，有助于预测其促瘤或抗瘤功能，并反映具有临床相关性的免疫动态。 **方法：** 我们分析了来自肺腺癌和三阴性乳腺癌队列的成像质谱流式数据。针对每一对免疫细胞，我们计算了一个相对距离评分，该评分量化了其与癌细胞空间邻近性的差异。我们通过将这些RD评分与细胞比例、密度及单个细胞距离等传统特征进行比较，评估了其预后和预测意义。为了考虑细胞丰度的变异，我们还推导了归一化的RD评分。 **结果：** RD评分与患者总生存期的关联性强于标准的免疫学指标。在所有免疫细胞对中，比较B细胞与中间型单核细胞邻近性的RD评分与改善的生存期关联最为显著。在三阴性乳腺癌中，RD评分也提高了对免疫化疗和化疗应答者与非应答者的区分能力。归一化的RD评分通过最小化细胞密度的影响并进一步突显免疫细胞空间关系的重要性，强化了这些发现。 **结论：** RD评分提供了一种空间信息化的生物标志物，在预测生存和治疗反应方面优于传统指标。该方法为理解肿瘤微环境中的免疫细胞行为提供了新视角，并具有指导个体化癌症治疗和患者分层的潜在应用价值。
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