Despite advances in treatment, lung cancer survival rates remain low. A better understanding of the cellular heterogeneity and interplay of cancer-associated fibroblasts (CAFs) within the tumor microenvironment will support the development of personalized therapies. We report a spatially resolved single-cell imaging mass cytometry (IMC) analysis of CAFs in a non-small cell lung cancer cohort of 1,070 patients. We identify four prognostic patient groups based on 11 CAF phenotypes with distinct spatial distributions and show that CAFs are independent prognostic factors for patient survival. The presence of tumor-like CAFs is strongly correlated with poor prognosis. In contrast, inflammatory CAFs and interferon-response CAFs are associated with inflamed tumor microenvironments and higher patient survival. High density of matrix CAFs is correlated with low immune infiltration and is negatively correlated with patient survival. In summary, our data identify phenotypic and spatial features of CAFs that are associated with patient outcome in NSCLC.

中文翻译：

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癌症相关成纤维细胞表型与非小细胞肺癌患者的预后相关

尽管治疗取得了进步，肺癌的存活率仍然很低。更好地了解肿瘤微环境中的细胞异质性和癌症相关成纤维细胞（CAF）的相互作用将支持个性化疗法的开发。我们报告了对 1,070 名非小细胞肺癌患者队列中 CAF 的空间分辨单细胞成像质谱流式分析 (IMC) 分析。我们根据具有不同空间分布的 11 种 CAF 表型确定了四个预后患者组，并表明 CAF 是患者生存的独立预后因素。肿瘤样 CAF 的存在与不良预后密切相关。相比之下，炎症性 CAF 和干扰素反应性 CAF 与发炎的肿瘤微环境和较高的患者生存率相关。高密度的基质 CAF 与低免疫浸润相关，并与患者存活率呈负相关。总之，我们的数据确定了与 NSCLC 患者预后相关的 CAF 的表型和空间特征。