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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| Format: | Article |
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Nature Portfolio
2025-08-01
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| 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. |
| format | Article |
| id | doaj-art-0725c209931e4767bd3ecb7db9350cec |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| 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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