Understanding the role of the tumour microenvironment (TME) in lung cancer is critical to improving patient outcome. We identified four histology-independent archetype TMEs in treatment-naive early-stage lung cancer using imaging mass cytometry in the TRACERx study (n=81 patients/198 samples/2.3million cells). In immune-hot adenocarcinomas, spatial niches of T cells and macrophages increased with clonal neoantigen burden, whereas such an increase was observed for niches of plasma and B cells in immune-excluded squamous cell carcinomas (LUSC). Immune-low TMEs were associated with fibroblast barriers to immune infiltration. The fourth archetype, characterised by sparse lymphocytes and high tumour-associated neutrophil (TAN) infiltration, had tumour cells spatially separated from vasculature and exhibited low spatial intratumour heterogeneity. TAN-High LUSC had frequent PIK3CA mutations. TAN-High tumours harboured recently expanded and metastasis-seeding subclones and had a shorter disease-free survival independent of stage. These findings delineate genomic, immune and physical barriers to immune surveillance and implicate neutrophil-rich TMEs in metastasis.

中文翻译：

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骨髓细胞和 T 细胞的空间结构协调肺癌的免疫逃避和临床结果

了解肿瘤微环境 (TME) 在肺癌中的作用对于改善患者预后至关重要。我们在 TRACERx 研究中使用成像质量流式细胞仪在未经治疗的早期肺癌中鉴定了四种与组织学无关的原型 TME（n = 81 名患者/198 个样本/230 万个细胞）。在免疫热腺癌中，T 细胞和巨噬细胞的空间生态位随着克隆新抗原负荷的增加而增加，而在免疫排除的鳞状细胞癌 (LUSC) 中，血浆和 B 细胞的空间生态位也出现这种增加。免疫低下的 TME 与免疫浸润的成纤维细胞屏障有关。第四种原型的特点是淋巴细胞稀疏和肿瘤相关中性粒细胞（TAN）浸润较高，肿瘤细胞在空间上与脉管系统分离，并表现出较低的肿瘤内空间异质性。 TAN-高 LUSC 具有频繁的 PIK3CA 突变。 TAN-高肿瘤含有最近扩增和转移的亚克隆，并且具有较短的无病生存期，与分期无关。这些发现描绘了免疫监视的基因组、免疫和物理障碍，并暗示富含中性粒细胞的 TME 与转移有关。