Department of Thoracic Surgery and Institute of Thoracic Oncology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu 610041, China.
Department of Thoracic Surgery and Institute of Thoracic Oncology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu 610041, China; Faculty of Dentistry, The University of Hong Kong, Prince Philip Dental Hospital, Sai Ying Pun, Hong Kong, China.
Cell Rep Med. 2024 Apr 16;5(4):101489. doi: 10.1016/j.xcrm.2024.101489. Epub 2024 Mar 29.
Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8 T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8 T cells, driven by specific stromal cells such as CTHCR1 fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8 T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.
肺腺癌是一种表现出广泛临床影像学表现的癌症，从磨玻璃密度（GGO）到纯实性结节，其生物学特征差异很大。我们目前对这种异质性的了解有限。为了解决这一差距，我们通过机器学习、单细胞 RNA 测序（scRNA-seq）和全外显子测序分析了 58 例肺腺癌患者，鉴定了与不同影像学模式和癌细胞状态相关的六种肺多细胞生态型（LMEs）。值得注意的是，早期癌症中与 GGO 相关的新抗原被 CD8 T 细胞识别，表明存在免疫激活环境，而实性结节则表现出免疫抑制的 LME，耗尽的 CD8 T 细胞由特定的基质细胞如 CTHCR1 成纤维细胞驱动。这项研究还强调了 GGO 样本中 EGFR（L858R）新抗原，提示潜在的 CD8 T 细胞激活。我们的发现为肺腺癌异质性提供了有价值的见解，为早期疾病的靶向治疗提供了新的途径。
Am J Respir Crit Care Med. 2021-11-15
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