Li Jian-Rong, Pan Xingxin, Lin Yupei, Zhao Yanding, Liu Yanhong, Li Yong, Amos Christopher I, Cheng Chao
Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX 77030, USA.
Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Cancers (Basel). 2025 Jul 14;17(14):2335. doi: 10.3390/cancers17142335.
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.
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).
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.
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（TME）通过塑造免疫反应和影响患者预后在癌症进展中起关键作用。我们假设，TME内特定免疫细胞对与癌细胞的相对接近程度有助于预测它们的促肿瘤或抗肿瘤功能，并反映临床相关的免疫动态。
我们分析了来自肺腺癌（LUAD）和三阴性乳腺癌（TNBC）队列的成像质谱流式细胞术（IMC）数据。对于每对免疫细胞，我们计算了一个相对距离（RD）分数，该分数量化了与癌细胞接近程度的空间差异。我们通过将这些RD分数与细胞分数、密度和单个细胞距离等传统特征进行比较，评估了它们的预后和预测意义。为了考虑细胞丰度的变化，我们还得出了标准化的RD分数（NRD分数）。
与标准免疫指标相比，RD分数与患者总体生存率的相关性更强。在所有免疫细胞对中，比较B细胞与中间单核细胞接近程度的RD分数与生存率提高的相关性最为显著。在TNBC中，RD分数也改善了免疫化疗和化疗反应者与无反应者之间的区分。标准化的RD分数通过最小化细胞密度的影响并进一步突出免疫细胞空间关系的重要性，强化了这些发现。
RD分数提供了一种基于空间信息的生物标志物，在预测生存和治疗反应方面优于传统指标。这种方法为TME中免疫细胞行为提供了新的视角，在指导个性化癌症治疗和患者分层方面具有潜在应用价值。
