德克萨斯大学Humam Kadara课题组的一项最新研究发现了多模态空间组学揭示肺泡祖细胞和促炎生态位在肺前体病变进展中的共同进化。这一研究成果发表在2025年11月6日出版的国际学术期刊《癌细胞》上。

该课题组人员生成了来自25名患者的56个人类前体病变和LUAD的空间转录组图，以及来自19名患者的36个病变的独立队列，共分析了486519个斑点和540万个细胞。研究小组确定了区分前体和LUAD的区域特定程序。空间分辨克隆结构揭示了LUAD前体进化的患者特异性异质性。小组发现上皮肺泡祖细胞表达肿瘤相关的元程序，并存在于富含促炎亚群（包括IL1B高巨噬细胞）的壁龛中。上皮促炎壁龛在前驱病变中普遍存在，但在LUAD中不太常见。这些小生境在小鼠体内是保守的，并促进肺泡祖细胞的生长。在癌前期单独靶向炎症或联合免疫检查点阻断可减少肺泡祖细胞。上皮炎性壁龛是阶段特异性的，塑造了早期LUAD的发展，代表了有希望的拦截目标。

研究人员表示，不同细胞亚群在肺腺癌（LUAD）前驱病变进展中的共同进化尚不完全清楚。

附：英文原文

Title: Multimodal spatial-omics reveal co-evolution of alveolar progenitors and proinflammatory niches in progression of lung precursor lesions

Author: Fuduan Peng, Ansam Sinjab, Yibo Dai, Warapen Treekitkarnmongkol, Sujuan Yang, Lorena I. Gomez Bolanos, Tieling Zhou, Minyue Chen, Alejandra G. Serrano, Avantika Krishna, Nastaran Karimi, Manvi Sharma, Akshay Basi, Guangsheng Pei, Jianlong Liao, Yunhe Liu, Jiping Feng, Zahraa Rahal, Yang Liu, Jiahui Jiang, Kai Yu, Tala Noun, Yuejiang Liu, Khaja Khan, Kyung Serk Cho, Jichao Chen, Luisa M. Solis, Sarah Mazzilli, Steven Dubinett, Tina Cascone, Avrum E. Spira, Stephen Swisher, Naoe Jimbo, Takuo Hayashi, Satsuki Kishikawa, Kazuya Takamochi, Tomoo Itoh, Takashi Yao, Kenji Suzuki, Neda Kalhor, Ignacio I. Wistuba, Mingyao Li, Seyed Javad Moghaddam, Junya Fujimoto, Jared Burks, Jeffrey Myers, Kadir Akdemir, Linghua Wang, Humam Kadara

Issue&Volume: 2025-11-06

Abstract: The co-evolution of different cell subsets in the progression of precursor lesions to lung adenocarcinoma (LUAD) is incompletely understood. We generated spatial transcriptomic maps of 56 human precursor lesions and LUADs from 25 patients and of an independent cohort of 36 lesions from 19 patients, analyzing a total of 486,519 spots and 5.4 million cells. We identify region-specific programs that distinguish precursors from LUADs. Spatially resolved clonal architectures reveal patient-specific heterogeneity in evolution of precursors to LUADs. We find epithelial alveolar progenitors expressing tumor-associated meta-programs and residing in niches enriched with proinflammatory subsets including IL1B high macrophages. Epithelial-proinflammatory niches are prevalent in precursor lesions but become less frequent in LUADs. These niches are conserved in mice and promote alveolar progenitor growth. Targeting inflammation alone or in combination with immune checkpoint blockade in precancerous phase reduces alveolar progenitors. Epithelial-inflammatory niches are stage-specific, shape early LUAD development and represent promising targets for interception.

DOI: 10.1016/j.ccell.2025.10.004

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00445-3