APOE-high myeloid cells are uniquely associated with metastatic intrathoracic lymph nodes obtained by EBUS-TBNA in primary lung cancer

Abstract The draining lymph node (LN) is the most frequent and often first site of cancer metastasis. Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is frequently performed as a standard practice in lung cancer diagnosis and staging, its diagnostic accuracy rem...

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Main Authors: Seung-jae Kim, Minhyung Kim, Ki-Hyun Kim, Jacob D. Eccles, Bumseo Baek, Catherine Dell, Kevin Haas, Christopher M. Kapp, Christian Ascoli, Sungyong You, Gye Young Park
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-01091-5
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author Seung-jae Kim
Minhyung Kim
Ki-Hyun Kim
Jacob D. Eccles
Bumseo Baek
Catherine Dell
Kevin Haas
Christopher M. Kapp
Christian Ascoli
Sungyong You
Gye Young Park
author_facet Seung-jae Kim
Minhyung Kim
Ki-Hyun Kim
Jacob D. Eccles
Bumseo Baek
Catherine Dell
Kevin Haas
Christopher M. Kapp
Christian Ascoli
Sungyong You
Gye Young Park
author_sort Seung-jae Kim
collection DOAJ
description Abstract The draining lymph node (LN) is the most frequent and often first site of cancer metastasis. Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is frequently performed as a standard practice in lung cancer diagnosis and staging, its diagnostic accuracy remains modest, primarily due to the minuscule sample size of needle aspirates. With the advent of single-cell technologies, we comprehensively analyzed the immune cell repertoire in a series of EBUS-TBNA samples. Intrathoracic LN samples from 18 subjects with pathologically confirmed metastasis and four controls without evidence of metastasis were compared using single-cell RNA sequencing and mass cytometry analyses. We found that immune cell composition and gene expression patterns differed markedly between metastatic and control LNs. In particular, metastatic LNs contained relatively more APOE-high myeloid cells, with the latter exhibiting significant transcriptional derangement and a powerful intercellular interaction signature. Additionally, CD8 T cells in metastatic LNs demonstrated a unique exhausted phenotype. In conclusion, immune cell phenotypes and gene expression patterns from EBUS-TBNA samples can be leveraged to advance our understanding of cancer immunology and may have independent diagnostic value when malignant cells fail to be identified on histopathology.
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spelling doaj-art-0725c209931e4767bd3ecb7db9350cec2025-08-24T11:05:48ZengNature Portfolionpj Precision Oncology2397-768X2025-08-019111410.1038/s41698-025-01091-5APOE-high myeloid cells are uniquely associated with metastatic intrathoracic lymph nodes obtained by EBUS-TBNA in primary lung cancerSeung-jae Kim0Minhyung Kim1Ki-Hyun Kim2Jacob D. Eccles3Bumseo Baek4Catherine Dell5Kevin Haas6Christopher M. Kapp7Christian Ascoli8Sungyong You9Gye Young Park10Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at ChicagoDepartments of Urology and Computational Biomedicine, Cedars-Sinai Medical CenterDivision of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at ChicagoDivision of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at ChicagoDivision of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at ChicagoJesse Brown Veterans Affairs Medical CenterDivision of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at ChicagoDivision of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at ChicagoDivision of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at ChicagoDepartments of Urology and Computational Biomedicine, Cedars-Sinai Medical CenterDivision of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at ChicagoAbstract The draining lymph node (LN) is the most frequent and often first site of cancer metastasis. Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is frequently performed as a standard practice in lung cancer diagnosis and staging, its diagnostic accuracy remains modest, primarily due to the minuscule sample size of needle aspirates. With the advent of single-cell technologies, we comprehensively analyzed the immune cell repertoire in a series of EBUS-TBNA samples. Intrathoracic LN samples from 18 subjects with pathologically confirmed metastasis and four controls without evidence of metastasis were compared using single-cell RNA sequencing and mass cytometry analyses. We found that immune cell composition and gene expression patterns differed markedly between metastatic and control LNs. In particular, metastatic LNs contained relatively more APOE-high myeloid cells, with the latter exhibiting significant transcriptional derangement and a powerful intercellular interaction signature. Additionally, CD8 T cells in metastatic LNs demonstrated a unique exhausted phenotype. In conclusion, immune cell phenotypes and gene expression patterns from EBUS-TBNA samples can be leveraged to advance our understanding of cancer immunology and may have independent diagnostic value when malignant cells fail to be identified on histopathology.https://doi.org/10.1038/s41698-025-01091-5
spellingShingle Seung-jae Kim
Minhyung Kim
Ki-Hyun Kim
Jacob D. Eccles
Bumseo Baek
Catherine Dell
Kevin Haas
Christopher M. Kapp
Christian Ascoli
Sungyong You
Gye Young Park
APOE-high myeloid cells are uniquely associated with metastatic intrathoracic lymph nodes obtained by EBUS-TBNA in primary lung cancer
npj Precision Oncology
title APOE-high myeloid cells are uniquely associated with metastatic intrathoracic lymph nodes obtained by EBUS-TBNA in primary lung cancer
title_full APOE-high myeloid cells are uniquely associated with metastatic intrathoracic lymph nodes obtained by EBUS-TBNA in primary lung cancer
title_fullStr APOE-high myeloid cells are uniquely associated with metastatic intrathoracic lymph nodes obtained by EBUS-TBNA in primary lung cancer
title_full_unstemmed APOE-high myeloid cells are uniquely associated with metastatic intrathoracic lymph nodes obtained by EBUS-TBNA in primary lung cancer
title_short APOE-high myeloid cells are uniquely associated with metastatic intrathoracic lymph nodes obtained by EBUS-TBNA in primary lung cancer
title_sort apoe high myeloid cells are uniquely associated with metastatic intrathoracic lymph nodes obtained by ebus tbna in primary lung cancer
url https://doi.org/10.1038/s41698-025-01091-5
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