Heterogeneity in the immune microenvironment of bone metastasis in driver‐positive non‐small cell lung cancer

Mutations in epidermal growth factor receptor and anaplastic lymphoma kinase are common driver events in non‐small cell lung cancer (NSCLC), which are associated with a high frequency of bone metastases (BMs). While the bone marrow represents a specialized immune microenvironment, the immune reperto...

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Veröffentlicht in:Molecular carcinogenesis 2023-07, Vol.62 (7), p.1001-1008
Hauptverfasser: Yang, Xiao‐Rong, Pi, Can, Zhang, Yi‐Chen, Chen, Zhi‐Hong, Zhang, Xu‐Chao, Zhu, Dong‐Qin, Yang, Ling‐Ling, Yin, Jiani C., Deng, Jia‐Yi, Yang, Ming‐Yi, Luo, Wei‐Chi, Wu, Yi‐Long, Zhou, Qing
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container_end_page 1008
container_issue 7
container_start_page 1001
container_title Molecular carcinogenesis
container_volume 62
creator Yang, Xiao‐Rong
Pi, Can
Zhang, Yi‐Chen
Chen, Zhi‐Hong
Zhang, Xu‐Chao
Zhu, Dong‐Qin
Yang, Ling‐Ling
Yin, Jiani C.
Deng, Jia‐Yi
Yang, Ming‐Yi
Luo, Wei‐Chi
Wu, Yi‐Long
Zhou, Qing
description Mutations in epidermal growth factor receptor and anaplastic lymphoma kinase are common driver events in non‐small cell lung cancer (NSCLC), which are associated with a high frequency of bone metastases (BMs). While the bone marrow represents a specialized immune microenvironment, the immune repertoire of BMs remains unknown. Considering the higher incidence of BMs in driver gene‐positive NSCLCs, and the unique biology of the bone, herein, we assessed the infiltrating immune cells and T cell receptor (TCR) profile of BMs in driver‐positive NSCLCs. Immune profile of BMs in driver gene‐positive NSCLC were assessed in 10 patients, where 6 had driver gene‐positive mutation. TCR and bulk RNA sequencing were performed on malignant bone samples. The diversity and clonality of the TCR repertoire were analyzed. The cellular components were inferred from bulk gene expression profiles computationally by CIBERSORT. Although BMs were generally regarded as immune‐cold tumors, immune cell composition analyses showed co‐existence of cytotoxic and suppressor immune cells in driver‐positive BM samples, as compared to primary lung. Analysis of the TCR repertoire indicated a trend of higher diversity and similar clonality in the driver‐positive compared with the driver‐negative subsets. In addition, we identified two cases that showed the opposite response to immune checkpoint blockade. A comparison of these two patients' BM samples showed more highly amplified clones, fewer M2 macrophages and more activated natural killer cells in the responder. In summary, BMs in NSCLC are heterogeneous in their immune microenvironment, which might be related to differential clinical outcomes to immune checkpoint blockade.
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While the bone marrow represents a specialized immune microenvironment, the immune repertoire of BMs remains unknown. Considering the higher incidence of BMs in driver gene‐positive NSCLCs, and the unique biology of the bone, herein, we assessed the infiltrating immune cells and T cell receptor (TCR) profile of BMs in driver‐positive NSCLCs. Immune profile of BMs in driver gene‐positive NSCLC were assessed in 10 patients, where 6 had driver gene‐positive mutation. TCR and bulk RNA sequencing were performed on malignant bone samples. The diversity and clonality of the TCR repertoire were analyzed. The cellular components were inferred from bulk gene expression profiles computationally by CIBERSORT. Although BMs were generally regarded as immune‐cold tumors, immune cell composition analyses showed co‐existence of cytotoxic and suppressor immune cells in driver‐positive BM samples, as compared to primary lung. Analysis of the TCR repertoire indicated a trend of higher diversity and similar clonality in the driver‐positive compared with the driver‐negative subsets. In addition, we identified two cases that showed the opposite response to immune checkpoint blockade. A comparison of these two patients' BM samples showed more highly amplified clones, fewer M2 macrophages and more activated natural killer cells in the responder. 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Analysis of the TCR repertoire indicated a trend of higher diversity and similar clonality in the driver‐positive compared with the driver‐negative subsets. In addition, we identified two cases that showed the opposite response to immune checkpoint blockade. A comparison of these two patients' BM samples showed more highly amplified clones, fewer M2 macrophages and more activated natural killer cells in the responder. 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Analysis of the TCR repertoire indicated a trend of higher diversity and similar clonality in the driver‐positive compared with the driver‐negative subsets. In addition, we identified two cases that showed the opposite response to immune checkpoint blockade. A comparison of these two patients' BM samples showed more highly amplified clones, fewer M2 macrophages and more activated natural killer cells in the responder. In summary, BMs in NSCLC are heterogeneous in their immune microenvironment, which might be related to differential clinical outcomes to immune checkpoint blockade.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37067398</pmid><doi>10.1002/mc.23541</doi><tpages>8</tpages></addata></record>
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identifier ISSN: 0899-1987
ispartof Molecular carcinogenesis, 2023-07, Vol.62 (7), p.1001-1008
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source Wiley Online Library - AutoHoldings Journals
subjects Bone marrow
bone metastasis
Clinical outcomes
Cytotoxicity
driver gene
Epidermal growth factor
Gene expression
Immune checkpoint inhibitors
Kinases
Lung cancer
Lymphocytes T
Macrophages
Metastases
Microenvironments
Mutation
Natural killer cells
Non-small cell lung carcinoma
NSCLC
Protein-tyrosine kinase
Small cell lung carcinoma
T cell receptors
TCR repertoire
tumor immune microenvironment
title Heterogeneity in the immune microenvironment of bone metastasis in driver‐positive non‐small cell lung cancer
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