Characteristics of the immunogenicity and tumor immune microenvironment in HER2-amplified lung adenocarcinoma
ObjectiveBesides breast and gastric cancer, HER2 amplification/mutation are also found in lung adenocarcinoma (LUAD). However, the correlation between HER2 variations and the phenotype of immunogenicity and tumor immune microenvironment (TIME) in LUAD compared with breast and gastric cancer has yet...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1042072/full |
| _version_ | 1828091079059046400 |
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| author | Qinyang Wang Ziyang Mao Wenyuan Li Shumei Wang Lei Wang Lin Chen Zhe Yang Xiaolan Fu Panpan Jiang Yixue Bai Longwen Xu Shirong Zhang Yuzhu Hou Xiaohui Jia Lili Jiang Mengjie Liu Guanjun Zhang Yina Jiang Hui Guo Hui Guo Hui Guo |
| author_facet | Qinyang Wang Ziyang Mao Wenyuan Li Shumei Wang Lei Wang Lin Chen Zhe Yang Xiaolan Fu Panpan Jiang Yixue Bai Longwen Xu Shirong Zhang Yuzhu Hou Xiaohui Jia Lili Jiang Mengjie Liu Guanjun Zhang Yina Jiang Hui Guo Hui Guo Hui Guo |
| author_sort | Qinyang Wang |
| collection | DOAJ |
| description | ObjectiveBesides breast and gastric cancer, HER2 amplification/mutation are also found in lung adenocarcinoma (LUAD). However, the correlation between HER2 variations and the phenotype of immunogenicity and tumor immune microenvironment (TIME) in LUAD compared with breast and gastric cancer has yet to be fully elucidated.MethodsWe integrated public databases (discovery set) and internal data (validated set) of 288 patients representing three distinct HER2-altered tumors. Genomic data were used to identify somatic mutations, copy number variations, and calculate tumor mutational burden (TMB) and microsatellite instability score. RNA sequencing was conducted to estimate immune gene signatures and contents of tumor-infiltrating immune cell populations. Finally, IHC was used to determine PD-L1 expression and the tumoral-infiltration of immune cells in 50 HER2-variant tumor specimens with no prior therapeutic regimens.ResultsCompared with HER2-amplified breast and gastric cancers, patients with HER2-amplified LUAD showed higher immunogenicity, mainly manifested in immune checkpoints expression and tissue/blood TMB. Additionally, HER2-amplified LUAD exhibited an inflamed TIME with remarkably increased genes encoding HLAs, T-cell activity and immune cell-type, and accompanied with tumor‐infiltrating lymphocytes. In LUAD, patients with HER2 amplification possessed higher tissue TMB than HER2 mutation, whereas no difference was observed in PD-L1 expression. HER2 amplification (primary) was associated with significantly higher PD-L1 expression and TMB than acquired HER2 amplification after resistance to EGFR-TKIs.ConclusionPatients with HER2-amplified LUAD have better immunogenicity and/or an inflamed TIME among HER2-aberrant tumors. Our study may provide clues for establishing the benefits and uses of ICIs for patients with this disease. |
| first_indexed | 2024-04-11T06:07:38Z |
| format | Article |
| id | doaj.art-72632b273aa14cef92ae37582a0450cc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T06:07:38Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-72632b273aa14cef92ae37582a0450cc2022-12-22T04:41:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10420721042072Characteristics of the immunogenicity and tumor immune microenvironment in HER2-amplified lung adenocarcinomaQinyang Wang0Ziyang Mao1Wenyuan Li2Shumei Wang3Lei Wang4Lin Chen5Zhe Yang6Xiaolan Fu7Panpan Jiang8Yixue Bai9Longwen Xu10Shirong Zhang11Yuzhu Hou12Xiaohui Jia13Lili Jiang14Mengjie Liu15Guanjun Zhang16Yina Jiang17Hui Guo18Hui Guo19Hui Guo20Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Pathology, Tangdu Hospital, The Second Affiliated Hospital of Air Force Military Medical University, Xi’an, ChinaDepartment of Thoracic Surgery, Tangdu Hospital, The Second Affiliated Hospital of Air Force Military Medical University, Xi’an, ChinaDepartment of Pathology, Shaanxi Provincial People’s Hospital, Xi’an, ChinaDepartment of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCentre for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaKey Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education of China, Xi’an, ChinaObjectiveBesides breast and gastric cancer, HER2 amplification/mutation are also found in lung adenocarcinoma (LUAD). However, the correlation between HER2 variations and the phenotype of immunogenicity and tumor immune microenvironment (TIME) in LUAD compared with breast and gastric cancer has yet to be fully elucidated.MethodsWe integrated public databases (discovery set) and internal data (validated set) of 288 patients representing three distinct HER2-altered tumors. Genomic data were used to identify somatic mutations, copy number variations, and calculate tumor mutational burden (TMB) and microsatellite instability score. RNA sequencing was conducted to estimate immune gene signatures and contents of tumor-infiltrating immune cell populations. Finally, IHC was used to determine PD-L1 expression and the tumoral-infiltration of immune cells in 50 HER2-variant tumor specimens with no prior therapeutic regimens.ResultsCompared with HER2-amplified breast and gastric cancers, patients with HER2-amplified LUAD showed higher immunogenicity, mainly manifested in immune checkpoints expression and tissue/blood TMB. Additionally, HER2-amplified LUAD exhibited an inflamed TIME with remarkably increased genes encoding HLAs, T-cell activity and immune cell-type, and accompanied with tumor‐infiltrating lymphocytes. In LUAD, patients with HER2 amplification possessed higher tissue TMB than HER2 mutation, whereas no difference was observed in PD-L1 expression. HER2 amplification (primary) was associated with significantly higher PD-L1 expression and TMB than acquired HER2 amplification after resistance to EGFR-TKIs.ConclusionPatients with HER2-amplified LUAD have better immunogenicity and/or an inflamed TIME among HER2-aberrant tumors. Our study may provide clues for establishing the benefits and uses of ICIs for patients with this disease.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1042072/fullHER2amplificationlung adenocarcinomaimmunogenicitytumor immune microenvironment |
| spellingShingle | Qinyang Wang Ziyang Mao Wenyuan Li Shumei Wang Lei Wang Lin Chen Zhe Yang Xiaolan Fu Panpan Jiang Yixue Bai Longwen Xu Shirong Zhang Yuzhu Hou Xiaohui Jia Lili Jiang Mengjie Liu Guanjun Zhang Yina Jiang Hui Guo Hui Guo Hui Guo Characteristics of the immunogenicity and tumor immune microenvironment in HER2-amplified lung adenocarcinoma Frontiers in Immunology HER2 amplification lung adenocarcinoma immunogenicity tumor immune microenvironment |
| title | Characteristics of the immunogenicity and tumor immune microenvironment in HER2-amplified lung adenocarcinoma |
| title_full | Characteristics of the immunogenicity and tumor immune microenvironment in HER2-amplified lung adenocarcinoma |
| title_fullStr | Characteristics of the immunogenicity and tumor immune microenvironment in HER2-amplified lung adenocarcinoma |
| title_full_unstemmed | Characteristics of the immunogenicity and tumor immune microenvironment in HER2-amplified lung adenocarcinoma |
| title_short | Characteristics of the immunogenicity and tumor immune microenvironment in HER2-amplified lung adenocarcinoma |
| title_sort | characteristics of the immunogenicity and tumor immune microenvironment in her2 amplified lung adenocarcinoma |
| topic | HER2 amplification lung adenocarcinoma immunogenicity tumor immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1042072/full |
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