Lung adenocarcinoma is the most common subtype of lung cancer, which has the second highest incidence among cancers. Immunotherapy has revolutionized lung cancer treatment, yet the checkpoint blockade response rate is less than 20% in patients with lung adenocarcinoma. As lung adenocarcinoma consists of heterogeneous histologic subsets with diverse tumor invasion phenotypes and clinical outcomes, understanding the mechanisms of resistance based on the histology subset is essential. In the current issue, Jang and colleagues demonstrated that PD-1–expressing macrophages are the dominant immune cell population in the tumor-immune microenvironment (TiME) of invasive lung adenocarcinoma and are responsible for driving tumor progression from preinvasive to invasive subtypes. PD-1–expressing macrophages are protumorigenic and highly plastic, potentially promoting invasive solid tumor development. Ablation of macrophages remodels the TiME and leads to a favorable anti-PD-1 blockade response, suggesting a potential combination therapy in patients with lung adenocarcinoma resistant to monotherapy. This current work highlights the spatiotemporal dynamics of the TiME during lung adenocarcinoma progression and the critical role of PD-1–expressing macrophages in driving tumorigenesis as well as resistance to immunotherapy. See related article by Jang et al., p. 2593

中文翻译：

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侵袭前到侵袭：表达 PD-1 的巨噬细胞使肺癌进入高速运转状态

肺腺癌是肺癌最常见的亚型，其发病率在癌症中位居第二。免疫疗法彻底改变了肺癌治疗，但肺腺癌患者的检查点阻断反应率低于 20%。由于肺腺癌由具有不同肿瘤侵袭表型和临床结果的异质组织学子集组成，因此基于组织学子集了解耐药机制至关重要。在本期中，Jang 及其同事证明，表达 PD-1 的巨噬细胞是侵袭性肺腺癌肿瘤免疫微环境 (TiME) 中的主要免疫细胞群，负责驱动肿瘤从侵袭前亚型进展为侵袭性亚型。表达 PD-1 的巨噬细胞具有促肿瘤性和高度可塑性，可能促进侵袭性实体瘤的发展。巨噬细胞的消融重塑了 TiME 并导致良好的抗 PD-1 阻断反应，这表明对单一疗法耐药的肺腺癌患者有潜在的联合疗法。目前的工作强调了肺腺癌进展过程中 TiME 的时空动态，以及表达 PD-1 的巨噬细胞在驱动肿瘤发生和免疫治疗耐药中的关键作用。参见 Jang 等人的相关文章，第 17 页。2593 目前的工作强调了肺腺癌进展过程中 TiME 的时空动态，以及表达 PD-1 的巨噬细胞在驱动肿瘤发生和免疫治疗耐药中的关键作用。参见 Jang 等人的相关文章，第 17 页。2593 目前的工作强调了肺腺癌进展过程中 TiME 的时空动态，以及表达 PD-1 的巨噬细胞在驱动肿瘤发生和免疫治疗耐药中的关键作用。参见 Jang 等人的相关文章，第 17 页。2593