Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma
Backgrounds Immunotherapy is less effective in patients with epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC). Lower programmed cell death-ligand 1 (PD-L1) expression and tumor mutation burden (TMB) are reported to be the underlying mechanism. Being another important...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2022-02-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/2/e003534.full |
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| author | Lei Yang Qing Zhou Bo Zhang Yi-Long Wu Zhi-Hong Chen Wen-zhao Zhong Fen Wang Yun-Ting He Song Dong Xue-Wu Wei Wei-Dong Chen Xiao-Rong Yang Xue-Meng Shang |
| author_facet | Lei Yang Qing Zhou Bo Zhang Yi-Long Wu Zhi-Hong Chen Wen-zhao Zhong Fen Wang Yun-Ting He Song Dong Xue-Wu Wei Wei-Dong Chen Xiao-Rong Yang Xue-Meng Shang |
| author_sort | Lei Yang |
| collection | DOAJ |
| description | Backgrounds Immunotherapy is less effective in patients with epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC). Lower programmed cell death-ligand 1 (PD-L1) expression and tumor mutation burden (TMB) are reported to be the underlying mechanism. Being another important factor to affect the efficacy of immunotherapy, tumor microenvironment (TME) characteristics of this subgroup of NSCLC are not comprehensively understood up to date. Hence, we initiated this study to describe the specific TME of EGFR-mutant lung adenocarcinoma (LUAD) from cellular compositional and functional perspectives to better understand the immune landscape of this most common subtype of NSCLC.Methods We used single-cell transcriptome sequencing and multiplex immunohistochemistry to investigate the immune microenvironment of EGFR-mutant and EGFR wild-type LUADs and determined the efficacy of immunotherapy. We analyzed single cells from nine treatment-naïve samples and compared them to three post-immunotherapy samples previously reported from single cell perspective using bioinformatics methods.Results We found that EGFR-mutant malignant epithelial cells had similar characteristics to the epithelial cells in non-responders. EGFR-mutant LUAD lacked CD8+ tissue-resident memory (TRM) cells, which could promote tertiary lymphoid structure generation by secreting CXCL13. In addition, other cell types, including tumor-associated macrophages and cancer-associated fibroblasts, which are capable of recruiting, retaining, and expanding CD8+ TRM cells in the TME, were also deficient in EGFR-mutant LUAD. Furthermore, EGFR-mutant LUAD had significantly less crosstalk between T cells and other cell types via programmed cell death-1 (PD-1) and PD-L1 or other immune checkpoints compared with EGFR wild-type LUAD.Conclusions Our findings provide a comprehensive understanding of the immune landscape of EGFR-mutant LUAD at the single-cell level. Based on the results, many cellular components might have negative impact on the specific TME of EGFR-mutant LUAD through influencing CD8+ TRM. Lack of CD8+ TRM might be a key factor responsible for the suppressive TME of EGFR-mutant LUAD. |
| format | Article |
| id | doaj-art-f65232bcc5bd44b6b92b0a93a6d4dfec |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2022-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-f65232bcc5bd44b6b92b0a93a6d4dfec2025-08-20T02:13:10ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-02-0110210.1136/jitc-2021-003534Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinomaLei Yang0Qing Zhou1Bo Zhang2Yi-Long Wu3Zhi-Hong Chen4Wen-zhao Zhong5Fen Wang6Yun-Ting He7Song Dong8Xue-Wu Wei9Wei-Dong Chen10Xiao-Rong Yang11Xue-Meng Shang121 Guangdong Lung Cancer Institute, Guangdong Provincial People`s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China4 Shanghai Xu Hui Mental Health Center, Shanghai, China1 Shanghai Eye Disease Prevention and Treatment Center, Shanghai, China6 Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People`s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People`s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China3Department of Gastroenterology, Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China1 Guangdong Lung Cancer Institute, Guangdong Provincial People`s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China1 Guangdong Lung Cancer Institute, Guangdong Provincial People`s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People`s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China3 Novel Bioinformatics Co, Shanghai, ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People`s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China4 Panovue Biological Technology Co, Beijing, ChinaBackgrounds Immunotherapy is less effective in patients with epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC). Lower programmed cell death-ligand 1 (PD-L1) expression and tumor mutation burden (TMB) are reported to be the underlying mechanism. Being another important factor to affect the efficacy of immunotherapy, tumor microenvironment (TME) characteristics of this subgroup of NSCLC are not comprehensively understood up to date. Hence, we initiated this study to describe the specific TME of EGFR-mutant lung adenocarcinoma (LUAD) from cellular compositional and functional perspectives to better understand the immune landscape of this most common subtype of NSCLC.Methods We used single-cell transcriptome sequencing and multiplex immunohistochemistry to investigate the immune microenvironment of EGFR-mutant and EGFR wild-type LUADs and determined the efficacy of immunotherapy. We analyzed single cells from nine treatment-naïve samples and compared them to three post-immunotherapy samples previously reported from single cell perspective using bioinformatics methods.Results We found that EGFR-mutant malignant epithelial cells had similar characteristics to the epithelial cells in non-responders. EGFR-mutant LUAD lacked CD8+ tissue-resident memory (TRM) cells, which could promote tertiary lymphoid structure generation by secreting CXCL13. In addition, other cell types, including tumor-associated macrophages and cancer-associated fibroblasts, which are capable of recruiting, retaining, and expanding CD8+ TRM cells in the TME, were also deficient in EGFR-mutant LUAD. Furthermore, EGFR-mutant LUAD had significantly less crosstalk between T cells and other cell types via programmed cell death-1 (PD-1) and PD-L1 or other immune checkpoints compared with EGFR wild-type LUAD.Conclusions Our findings provide a comprehensive understanding of the immune landscape of EGFR-mutant LUAD at the single-cell level. Based on the results, many cellular components might have negative impact on the specific TME of EGFR-mutant LUAD through influencing CD8+ TRM. Lack of CD8+ TRM might be a key factor responsible for the suppressive TME of EGFR-mutant LUAD.https://jitc.bmj.com/content/10/2/e003534.full |
| spellingShingle | Lei Yang Qing Zhou Bo Zhang Yi-Long Wu Zhi-Hong Chen Wen-zhao Zhong Fen Wang Yun-Ting He Song Dong Xue-Wu Wei Wei-Dong Chen Xiao-Rong Yang Xue-Meng Shang Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma Journal for ImmunoTherapy of Cancer |
| title | Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma |
| title_full | Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma |
| title_fullStr | Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma |
| title_full_unstemmed | Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma |
| title_short | Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma |
| title_sort | single cell transcriptome analysis revealed a suppressive tumor immune microenvironment in egfr mutant lung adenocarcinoma |
| url | https://jitc.bmj.com/content/10/2/e003534.full |
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