Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer-related mortality worldwide. Tumour ecosystems feature diverse immune cell types. Myeloid cells, in particular, are prevalent and have a well-established role in promoting the disease. In our study, we profile approximately 900,000 cells from 25 treatment-naive patients with adenocarcinoma and squamous-cell carcinoma by single-cell and spatial transcriptomics. We note an inverse relationship between anti-inflammatory macrophages and NK cells/T cells, and with reduced NK cell cytotoxicity within the tumour. While we observe a similar cell type composition in both adenocarcinoma and squamous-cell carcinoma, we detect significant differences in the co-expression of various immune checkpoint inhibitors. Moreover, we reveal evidence of a transcriptional “reprogramming” of macrophages in tumours, shifting them towards cholesterol export and adopting a foetal-like transcriptional signature which promotes iron efflux. Our multi-omic resource offers a high-resolution molecular map of tumour-associated macrophages, enhancing our understanding of their role within the tumour microenvironment.

肺癌是第二常见的癌症，也是全球癌症相关死亡的主要原因。肿瘤生态系统具有多种免疫细胞类型。骨髓细胞尤其普遍，并且在促进该疾病方面具有明确的作用。在我们的研究中，我们通过单细胞和空间转录组学分析了来自 25 名未经治疗的腺癌和鳞状细胞癌患者的约 900,000 个细胞。我们注意到抗炎巨噬细胞和 NK 细胞/T 细胞之间存在负相关关系，并且肿瘤内 NK 细胞的细胞毒性降低。虽然我们在腺癌和鳞状细胞癌中观察到相似的细胞类型组成，但我们发现各种免疫检查点抑制剂的共表达存在显着差异。此外，我们揭示了肿瘤中巨噬细胞转录“重编程”的证据，将它们转向胆固醇输出，并采用促进铁流出的胎儿样转录特征。我们的多组学资源提供了肿瘤相关巨噬细胞的高分辨率分子图，增强了我们对其在肿瘤微环境中的作用的理解。