{"_":"CSF1肿瘤细胞-SPP1巨噬细胞轴驱动胃癌进展和免疫治疗耐药。","sup":["+","+"]}
{"_":"The CSF1 tumor cell-SPP1 macrophage axis drives gastric cancer progression and immunotherapy resistance.","sup":["+","+"]}
摘要(中文译文)
胃癌（GC）仍是全球癌症死亡的主要原因之一，具有显著的异质性。尽管免疫检查点阻断（ICB）已成为一种有前景的策略，但普遍存在的耐药性常常限制其临床疗效。阐明驱动这种耐药的机制并识别预测性生物标志物，仍是实现胃癌精准肿瘤学的关键挑战。我们通过整合胃癌患者的单细胞RNA测序（scRNA-seq）数据与公共空间转录组学（ST）数据，构建了空间多组学图谱。对独立免疫治疗队列进行计算解卷积，以确定与ICB疗效相关的特定巨噬细胞和成纤维细胞亚群。通过细胞间通讯和ST分析表征了细胞间免疫抑制信号及空间邻近关系。我们利用非接触共培养系统和对独立临床队列的多重免疫组化（mIHC）分析，验证了该交互作用的生物学意义。我们通过整合131,027个细胞的scRNA-seq与空间转录组学，构建了空间分辨的多组学图谱。免疫治疗队列的解卷积分析发现，在ICB疗效较差的肿瘤中，SPP1+巨噬细胞和MFAP5+成纤维细胞同步富集。空间分析量化了产生CSF1的恶性细胞与SPP1巨噬细胞之间显著的空间共定位。在实验上，恶性细胞来源的CSF1诱导了SPP1+巨噬细胞极化，触发了 和 的协同上调。通过分泌组分析和功能实验证实，这种交互作用显著增强了胃癌细胞的集落形成和侵袭潜能。最后，mIHC染色验证了临床肿瘤组织中CSF1+恶性细胞与SPP1+巨噬细胞的共定位。我们的研究确定了一个由CSF1+恶性细胞和SPP1+巨噬细胞构成的空间组织生态位，是胃癌ICB耐药的关键驱动因素。通过界定这两种细胞类型之间由CSF1介导的交互作用，这些发现突出了增强免疫治疗疗效的有前景的治疗靶点。
Abstract
Gastric cancer (GC) remains a leading cause of global cancer mortality, characterized by profound heterogeneity. While immune checkpoint blockade (ICB) has emerged as a promising strategy, pervasive resistance frequently limits its clinical efficacy. Elucidating the mechanisms driving this resistance and identifying predictive biomarkers remain critical challenges for achieving precision oncology in GC. We constructed a spatial multi-omic atlas by integrating scRNA-seq from GC patients with public spatial transcriptomics (ST) data. Computational deconvolution of independent immunotherapy cohorts was performed to pinpoint specific macrophage and fibroblast subsets linked to ICB efficacy. Intercellular immunosuppressive signaling and spatial proximity were characterized via cell-cell communication and ST analysis. We validated the biological significance of this crosstalk using non-contact co-culture systems and mIHC analysis of an independent clinical cohort. We constructed a spatially resolved multi-omic atlas by integrating scRNA-seq from 131,027 cells with spatial transcriptomics. Deconvolution of immunotherapy cohorts identified the synchronous enrichment of SPP1+macrophages and MFAP5+fibroblasts in tumors with poor ICB efficacy. Spatial analysis quantified a significant co-localization between CSF1-producing malignant cells and SPP1 macrophages. Experimentally, malignant cell-derived CSF1 induced SPP1+ macrophage polarization, triggering the synergistic upregulation of and . This crosstalk significantly enhanced GC cell colony formation and invasive potential, as confirmed by secretome profiling and functional assays. Finally, mIHC staining validated the co-localization of CSF1+malignant cells and SPP1+macrophages within clinical tumor tissues. Our study identifies a spatially organized niche involving CSF1+malignant cells and SPP1+ macrophages as a key driver of ICB resistance in GC. By defining the CSF1-mediated crosstalk between these two cell types, these findings highlight promising therapeutic targets to enhance the efficacy of immunotherapy.
如何引用
AMA
Heng Zhang, Yundong You, Jinhao Peng, Qinhao Du, Xifan Liu. {"_":"The CSF1 tumor cell-SPP1 macrophage axis drives gastric cancer progression and immunotherapy resistance.","sup":["+","+"]}. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1817573.
APA
Heng Zhang, Yundong You, Jinhao Peng, Qinhao Du, Xifan Liu (2026). {"_":"The CSF1 tumor cell-SPP1 macrophage axis drives gastric cancer progression and immunotherapy resistance.","sup":["+","+"]}. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1817573
GB/T 7714
Heng Zhang, Yundong You, Jinhao Peng, Qinhao Du, Xifan Liu. {"_":"The CSF1 tumor cell-SPP1 macrophage axis drives gastric cancer progression and immunotherapy resistance.","sup":["+","+"]}[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1817573.
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