Tumor Microenvironment Profiling Identifies Prognostic Signatures and Suggests Immunotherapeutic Benefits in Neuroblastoma
The tumor microenvironment (TME) influences disease initiation and progression. Cross-talks of cells within TME can affect the efficacy of immunotherapies. However, a precise, concise, and comprehensive TME landscape in neuroblastoma (NB) has not been established. Here, we profiled the TME landscape...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.814836/full |
| _version_ | 1817991714723332096 |
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| author | Chenzhao Feng Ting Li Jun Xiao Jing Wang Xinyao Meng Huizhong Niu Bin Jiang Lei Huang Xiaogeng Deng Xueqiang Yan Dianming Wu Yifan Fang Yu Lin Feng Chen Xiaojuan Wu Xiang Zhao Jiexiong Feng |
| author_facet | Chenzhao Feng Ting Li Jun Xiao Jing Wang Xinyao Meng Huizhong Niu Bin Jiang Lei Huang Xiaogeng Deng Xueqiang Yan Dianming Wu Yifan Fang Yu Lin Feng Chen Xiaojuan Wu Xiang Zhao Jiexiong Feng |
| author_sort | Chenzhao Feng |
| collection | DOAJ |
| description | The tumor microenvironment (TME) influences disease initiation and progression. Cross-talks of cells within TME can affect the efficacy of immunotherapies. However, a precise, concise, and comprehensive TME landscape in neuroblastoma (NB) has not been established. Here, we profiled the TME landscape of 498 NB-related patients on a self-curated gene list and identified three prognostic TMEsubgroups. The differentially expressed genes in these three TMEsubgroups were used to construct a genetic signature of the TME landscape and characterize three GeneSubgroups. The subgroup with the worst overall survival prognosis, the TMEsubgroup/GeneSubgroup3, lacked immune cell infiltration and received the highest scores of MYCN- and ALK-related signatures and lowest scores of immune pathways. Additionally, we found that the GeneSubgroup3 might be benefited from anti-GD2 instead of anti-PD-1 therapy. We further created a 48-gene signature, the TMEscore, to infer prognosis and validated it in three independent NB cohorts and a pan-cancer cohort of 9,460 patients. We did RNA-seq on 16 samples and verified that TMEscore was higher in patients with stage 3/4 than stage 1/2 diseases. The TMEscore could also predict responses for several immunotherapies. After adding clinical features, we found that the nomogram-based score system, the TMEIndex, surpassed the current risk system at predicting survivals. Our analysis explained TME at the transcriptome level and paved the way for immunotherapies in NB. |
| first_indexed | 2024-04-14T01:16:58Z |
| format | Article |
| id | doaj.art-94be50cb6a20445c996b45d6f52db022 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-14T01:16:58Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-94be50cb6a20445c996b45d6f52db0222022-12-22T02:20:49ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-04-011010.3389/fcell.2022.814836814836Tumor Microenvironment Profiling Identifies Prognostic Signatures and Suggests Immunotherapeutic Benefits in NeuroblastomaChenzhao Feng0Ting Li1Jun Xiao2Jing Wang3Xinyao Meng4Huizhong Niu5Bin Jiang6Lei Huang7Xiaogeng Deng8Xueqiang Yan9Dianming Wu10Yifan Fang11Yu Lin12Feng Chen13Xiaojuan Wu14Xiang Zhao15Jiexiong Feng16Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of General Surgery, Children’s Hospital of Hebei Province, Shijiazhuang, ChinaDepartment of General Surgery, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Pediatric Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Pediatric Surgery, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatric Surgery, Fujian Provincial Maternity and Children’s Hospital, Fuzhou, ChinaDepartment of Pediatric Surgery, Fujian Provincial Maternity and Children’s Hospital, Fuzhou, ChinaDepartment of Pediatric Surgery, Fujian Provincial Maternity and Children’s Hospital, Fuzhou, ChinaDepartment of Pediatric Surgery, Fujian Medical University Union Hospital, Fuzhou, ChinaDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaThe tumor microenvironment (TME) influences disease initiation and progression. Cross-talks of cells within TME can affect the efficacy of immunotherapies. However, a precise, concise, and comprehensive TME landscape in neuroblastoma (NB) has not been established. Here, we profiled the TME landscape of 498 NB-related patients on a self-curated gene list and identified three prognostic TMEsubgroups. The differentially expressed genes in these three TMEsubgroups were used to construct a genetic signature of the TME landscape and characterize three GeneSubgroups. The subgroup with the worst overall survival prognosis, the TMEsubgroup/GeneSubgroup3, lacked immune cell infiltration and received the highest scores of MYCN- and ALK-related signatures and lowest scores of immune pathways. Additionally, we found that the GeneSubgroup3 might be benefited from anti-GD2 instead of anti-PD-1 therapy. We further created a 48-gene signature, the TMEscore, to infer prognosis and validated it in three independent NB cohorts and a pan-cancer cohort of 9,460 patients. We did RNA-seq on 16 samples and verified that TMEscore was higher in patients with stage 3/4 than stage 1/2 diseases. The TMEscore could also predict responses for several immunotherapies. After adding clinical features, we found that the nomogram-based score system, the TMEIndex, surpassed the current risk system at predicting survivals. Our analysis explained TME at the transcriptome level and paved the way for immunotherapies in NB.https://www.frontiersin.org/articles/10.3389/fcell.2022.814836/fullneuroblastomatumor microenvironmentimmunotherapypan-cancerpediatric cancer |
| spellingShingle | Chenzhao Feng Ting Li Jun Xiao Jing Wang Xinyao Meng Huizhong Niu Bin Jiang Lei Huang Xiaogeng Deng Xueqiang Yan Dianming Wu Yifan Fang Yu Lin Feng Chen Xiaojuan Wu Xiang Zhao Jiexiong Feng Tumor Microenvironment Profiling Identifies Prognostic Signatures and Suggests Immunotherapeutic Benefits in Neuroblastoma Frontiers in Cell and Developmental Biology neuroblastoma tumor microenvironment immunotherapy pan-cancer pediatric cancer |
| title | Tumor Microenvironment Profiling Identifies Prognostic Signatures and Suggests Immunotherapeutic Benefits in Neuroblastoma |
| title_full | Tumor Microenvironment Profiling Identifies Prognostic Signatures and Suggests Immunotherapeutic Benefits in Neuroblastoma |
| title_fullStr | Tumor Microenvironment Profiling Identifies Prognostic Signatures and Suggests Immunotherapeutic Benefits in Neuroblastoma |
| title_full_unstemmed | Tumor Microenvironment Profiling Identifies Prognostic Signatures and Suggests Immunotherapeutic Benefits in Neuroblastoma |
| title_short | Tumor Microenvironment Profiling Identifies Prognostic Signatures and Suggests Immunotherapeutic Benefits in Neuroblastoma |
| title_sort | tumor microenvironment profiling identifies prognostic signatures and suggests immunotherapeutic benefits in neuroblastoma |
| topic | neuroblastoma tumor microenvironment immunotherapy pan-cancer pediatric cancer |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.814836/full |
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