An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategy
BackgroundThis study aimed to develop a vaccine that targets mutation-derived neoantigen in Chinese non-small-cell lung cancer (NSCLC).MethodsA cohort of 1862 Chinese NSCLC patients who underwent targeted sequencing with a 1021-gene panel was investigated. HLA typing was done using OptiType v1.0 and...
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Frontiers Media S.A.
2022-11-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1022598/full |
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| author | Jing Lin Jing Lin Jun Liu Jun Liu Shi-guang Hao Bin Lan Bin Lan Xiao-bin Zheng Jia-ni Xiong Jia-ni Xiong Ying-qian Zhang Xuan Gao Xuan Gao Chuan-ben Chen Chuan-ben Chen Ling Chen Ling Chen Yu-fang Huang Yu-fang Huang Hong Luo Hong Luo Yu-ting Yi Xin Yi Jian-ping Lu Jian-ping Lu Xiong-wei Zheng Xiong-wei Zheng Gang Chen Gang Chen Xue-feng Wang Xue-feng Wang Xue-feng Wang Yu Chen Yu Chen |
| author_facet | Jing Lin Jing Lin Jun Liu Jun Liu Shi-guang Hao Bin Lan Bin Lan Xiao-bin Zheng Jia-ni Xiong Jia-ni Xiong Ying-qian Zhang Xuan Gao Xuan Gao Chuan-ben Chen Chuan-ben Chen Ling Chen Ling Chen Yu-fang Huang Yu-fang Huang Hong Luo Hong Luo Yu-ting Yi Xin Yi Jian-ping Lu Jian-ping Lu Xiong-wei Zheng Xiong-wei Zheng Gang Chen Gang Chen Xue-feng Wang Xue-feng Wang Xue-feng Wang Yu Chen Yu Chen |
| author_sort | Jing Lin |
| collection | DOAJ |
| description | BackgroundThis study aimed to develop a vaccine that targets mutation-derived neoantigen in Chinese non-small-cell lung cancer (NSCLC).MethodsA cohort of 1862 Chinese NSCLC patients who underwent targeted sequencing with a 1021-gene panel was investigated. HLA typing was done using OptiType v1.0 and neoantigens were predicted by netMHCpan v4.0. HLA LOH was inferred using the lohhla algorithm and TMB were quantified by counting the total number of non-synonymous ones based on our panel data. CIBERSORT was utilized to estimate the TME in different EGFR mutant subtype by using TCGA data.ResultsHLA-A*11:01(42.59%) was the top one allele and HLA-A*33:03(12.94%) ranked 12th. EGFR L858R (22.61%) was the most prevalent gene variant. The binding affinity (IC50 MT = 22.9 nM) and shared frequency (2.93%) of EGFR L858R in combination with HLA-A*33:03 were optimal. In a subsequent further analysis on immunological features of EGFR mutant subtypes, 63.1% HLA loss of heterozygosity LOH (HLA LOH) and 0.37% (7 of 1862) B2M aberrations were found in our population, both had no significant association with EGFR mutant subtypes suggesting that the process of antigen presentation involved HLA LOH and B2M mechanisms in EGFR L858R is working. Tumor mutation burden (TMB) was investigated by utilizing our panel and showed that EGFR L858R had the lowest TMB compared with other EGFR mutant subtypes. In addition, analysis of 22 immune cell types from The Cancer Genome Atlas (TCGA) data showed EGFR L858R was correlated with low level of CD8 T cells, activated CD4 memory T cells and elevated level of macrophage M2 suggesting an inhibited tumor microenvironment (TME).ConclusionOur study identified that EGFR L858R neoantigen had the potential to generate cancer vaccines in NSCLC patients with HLA A*33:03. The neoantigen-based vaccines may become an effective salvage regimen for EGFR L858R subgroup after targeted therapy or immune checkpoint inhibitors (ICIs) failure. |
| first_indexed | 2024-04-11T15:41:05Z |
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| language | English |
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| publishDate | 2022-11-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-2120231c800146d5ab277713885b52c62022-12-22T04:15:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10225981022598An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategyJing Lin0Jing Lin1Jun Liu2Jun Liu3Shi-guang Hao4Bin Lan5Bin Lan6Xiao-bin Zheng7Jia-ni Xiong8Jia-ni Xiong9Ying-qian Zhang10Xuan Gao11Xuan Gao12Chuan-ben Chen13Chuan-ben Chen14Ling Chen15Ling Chen16Yu-fang Huang17Yu-fang Huang18Hong Luo19Hong Luo20Yu-ting Yi21Xin Yi22Jian-ping Lu23Jian-ping Lu24Xiong-wei Zheng25Xiong-wei Zheng26Gang Chen27Gang Chen28Xue-feng Wang29Xue-feng Wang30Xue-feng Wang31Yu Chen32Yu Chen33Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaCancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaDepartment of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaCancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaGeneplus-Beijing Institute, Beijing, ChinaDepartment of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaFujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaFujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaDepartment of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaCancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaGeneplus-Beijing Institute, Beijing, ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaDepartment of Translational Medicine, GenePlus- Shenzhen Clinical Laboratory, ShenZhen, ChinaCancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaDepartment of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaDepartment of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaCancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaDepartment of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaCancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaDepartment of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaCancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaGeneplus-Beijing Institute, Beijing, ChinaGeneplus-Beijing Institute, Beijing, ChinaCancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaDepartment of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaCancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaDepartment of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaCancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaDepartment of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaDepartment of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaFujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaThe Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou, ChinaDepartment of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaCancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, ChinaBackgroundThis study aimed to develop a vaccine that targets mutation-derived neoantigen in Chinese non-small-cell lung cancer (NSCLC).MethodsA cohort of 1862 Chinese NSCLC patients who underwent targeted sequencing with a 1021-gene panel was investigated. HLA typing was done using OptiType v1.0 and neoantigens were predicted by netMHCpan v4.0. HLA LOH was inferred using the lohhla algorithm and TMB were quantified by counting the total number of non-synonymous ones based on our panel data. CIBERSORT was utilized to estimate the TME in different EGFR mutant subtype by using TCGA data.ResultsHLA-A*11:01(42.59%) was the top one allele and HLA-A*33:03(12.94%) ranked 12th. EGFR L858R (22.61%) was the most prevalent gene variant. The binding affinity (IC50 MT = 22.9 nM) and shared frequency (2.93%) of EGFR L858R in combination with HLA-A*33:03 were optimal. In a subsequent further analysis on immunological features of EGFR mutant subtypes, 63.1% HLA loss of heterozygosity LOH (HLA LOH) and 0.37% (7 of 1862) B2M aberrations were found in our population, both had no significant association with EGFR mutant subtypes suggesting that the process of antigen presentation involved HLA LOH and B2M mechanisms in EGFR L858R is working. Tumor mutation burden (TMB) was investigated by utilizing our panel and showed that EGFR L858R had the lowest TMB compared with other EGFR mutant subtypes. In addition, analysis of 22 immune cell types from The Cancer Genome Atlas (TCGA) data showed EGFR L858R was correlated with low level of CD8 T cells, activated CD4 memory T cells and elevated level of macrophage M2 suggesting an inhibited tumor microenvironment (TME).ConclusionOur study identified that EGFR L858R neoantigen had the potential to generate cancer vaccines in NSCLC patients with HLA A*33:03. The neoantigen-based vaccines may become an effective salvage regimen for EGFR L858R subgroup after targeted therapy or immune checkpoint inhibitors (ICIs) failure.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1022598/fullEGFR L858R mutationneoantigen vaccineHLA A*33:03immunological featuresChinese NSCLC |
| spellingShingle | Jing Lin Jing Lin Jun Liu Jun Liu Shi-guang Hao Bin Lan Bin Lan Xiao-bin Zheng Jia-ni Xiong Jia-ni Xiong Ying-qian Zhang Xuan Gao Xuan Gao Chuan-ben Chen Chuan-ben Chen Ling Chen Ling Chen Yu-fang Huang Yu-fang Huang Hong Luo Hong Luo Yu-ting Yi Xin Yi Jian-ping Lu Jian-ping Lu Xiong-wei Zheng Xiong-wei Zheng Gang Chen Gang Chen Xue-feng Wang Xue-feng Wang Xue-feng Wang Yu Chen Yu Chen An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategy Frontiers in Immunology EGFR L858R mutation neoantigen vaccine HLA A*33:03 immunological features Chinese NSCLC |
| title | An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategy |
| title_full | An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategy |
| title_fullStr | An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategy |
| title_full_unstemmed | An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategy |
| title_short | An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategy |
| title_sort | egfr l858r mutation identified in 1862 chinese nsclc patients can be a promising neoantigen vaccine therapeutic strategy |
| topic | EGFR L858R mutation neoantigen vaccine HLA A*33:03 immunological features Chinese NSCLC |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1022598/full |
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