Immune Landscape of the Tumor Microenvironment Identifies Prognostic Gene Signature CD4/CD68/CSF1R in Osteosarcoma
Background: Osteosarcoma (OSA), the most common primary bone malignancy in children and adolescents, is prone to metastases and unfavorable prognosis. Owing to its strong genomic heterogeneity, traditional chemotherapy, or targeted immunotherapy has not effectively improved the related overall survi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.01198/full |
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| author | Yi-jiang Song Yi-jiang Song Yanyang Xu Yanyang Xu Xiaojun Zhu Xiaojun Zhu Jianchang Fu Jianchang Fu Chuangzhong Deng Chuangzhong Deng Hongmin Chen Hongmin Chen Huaiyuan Xu Huaiyuan Xu Guohui Song Guohui Song Jinchang Lu Jinchang Lu Qinglian Tang Qinglian Tang Jin Wang Jin Wang |
| author_facet | Yi-jiang Song Yi-jiang Song Yanyang Xu Yanyang Xu Xiaojun Zhu Xiaojun Zhu Jianchang Fu Jianchang Fu Chuangzhong Deng Chuangzhong Deng Hongmin Chen Hongmin Chen Huaiyuan Xu Huaiyuan Xu Guohui Song Guohui Song Jinchang Lu Jinchang Lu Qinglian Tang Qinglian Tang Jin Wang Jin Wang |
| author_sort | Yi-jiang Song |
| collection | DOAJ |
| description | Background: Osteosarcoma (OSA), the most common primary bone malignancy in children and adolescents, is prone to metastases and unfavorable prognosis. Owing to its strong genomic heterogeneity, traditional chemotherapy, or targeted immunotherapy has not effectively improved the related overall survival for decades. Since the landscape of the OSA tumor immune microenvironment is scarcely known, despite it playing a crucial role in predicting clinical outcomes and therapeutic efficacies, we aimed to elucidate its molecular characteristics.Methods: The immune signature of 101 OSA samples was explored using transcriptome profiling and clinical characteristics retrieved from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program. Correlations between the prognostic immune markers and their clinical chemotherapy responses were assessed and verified based on 45 OSA primary tumors.Findings: We identified the heterogeneity underlying tumor immune signature in OSA, and found CD4+ T cells and macrophage markers CD4/IFNGR2/CD68 to be feasible prognostic factors, exerting significantly positive correlation with each other. Specifically, CSF1R, which plays an essential role in the regulation of proliferation and differentiation of macrophages, was found to be a specific signature associated with CD4/CD68, with improved OSA clinical outcomes.Interpretation: The immune landscape based on CD4/CD68/CSF1R gene signatures showed considerable promise for prognostic and therapeutic stratification in OSA patients. A specific immune signature for OSA, abundantly consisting of Th1-polarized CD4+ T cells and CSF1R-related CD68+ macrophages, may improve the predictive efficacy of chemotherapy and improve prognosis in patients with OSA. |
| first_indexed | 2024-12-12T15:33:54Z |
| format | Article |
| id | doaj.art-fbddf7975619425998dd07e57b021335 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T15:33:54Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-fbddf7975619425998dd07e57b0213352022-12-22T00:20:03ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-07-011010.3389/fonc.2020.01198542604Immune Landscape of the Tumor Microenvironment Identifies Prognostic Gene Signature CD4/CD68/CSF1R in OsteosarcomaYi-jiang Song0Yi-jiang Song1Yanyang Xu2Yanyang Xu3Xiaojun Zhu4Xiaojun Zhu5Jianchang Fu6Jianchang Fu7Chuangzhong Deng8Chuangzhong Deng9Hongmin Chen10Hongmin Chen11Huaiyuan Xu12Huaiyuan Xu13Guohui Song14Guohui Song15Jinchang Lu16Jinchang Lu17Qinglian Tang18Qinglian Tang19Jin Wang20Jin Wang21Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, ChinaBackground: Osteosarcoma (OSA), the most common primary bone malignancy in children and adolescents, is prone to metastases and unfavorable prognosis. Owing to its strong genomic heterogeneity, traditional chemotherapy, or targeted immunotherapy has not effectively improved the related overall survival for decades. Since the landscape of the OSA tumor immune microenvironment is scarcely known, despite it playing a crucial role in predicting clinical outcomes and therapeutic efficacies, we aimed to elucidate its molecular characteristics.Methods: The immune signature of 101 OSA samples was explored using transcriptome profiling and clinical characteristics retrieved from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program. Correlations between the prognostic immune markers and their clinical chemotherapy responses were assessed and verified based on 45 OSA primary tumors.Findings: We identified the heterogeneity underlying tumor immune signature in OSA, and found CD4+ T cells and macrophage markers CD4/IFNGR2/CD68 to be feasible prognostic factors, exerting significantly positive correlation with each other. Specifically, CSF1R, which plays an essential role in the regulation of proliferation and differentiation of macrophages, was found to be a specific signature associated with CD4/CD68, with improved OSA clinical outcomes.Interpretation: The immune landscape based on CD4/CD68/CSF1R gene signatures showed considerable promise for prognostic and therapeutic stratification in OSA patients. A specific immune signature for OSA, abundantly consisting of Th1-polarized CD4+ T cells and CSF1R-related CD68+ macrophages, may improve the predictive efficacy of chemotherapy and improve prognosis in patients with OSA.https://www.frontiersin.org/article/10.3389/fonc.2020.01198/fullosteosarcomatumor immune microenvironmentprognostic gene signaturetumor infiltrating immune cellstumor-associated macrophagestumor-infiltrating lymphocytes |
| spellingShingle | Yi-jiang Song Yi-jiang Song Yanyang Xu Yanyang Xu Xiaojun Zhu Xiaojun Zhu Jianchang Fu Jianchang Fu Chuangzhong Deng Chuangzhong Deng Hongmin Chen Hongmin Chen Huaiyuan Xu Huaiyuan Xu Guohui Song Guohui Song Jinchang Lu Jinchang Lu Qinglian Tang Qinglian Tang Jin Wang Jin Wang Immune Landscape of the Tumor Microenvironment Identifies Prognostic Gene Signature CD4/CD68/CSF1R in Osteosarcoma Frontiers in Oncology osteosarcoma tumor immune microenvironment prognostic gene signature tumor infiltrating immune cells tumor-associated macrophages tumor-infiltrating lymphocytes |
| title | Immune Landscape of the Tumor Microenvironment Identifies Prognostic Gene Signature CD4/CD68/CSF1R in Osteosarcoma |
| title_full | Immune Landscape of the Tumor Microenvironment Identifies Prognostic Gene Signature CD4/CD68/CSF1R in Osteosarcoma |
| title_fullStr | Immune Landscape of the Tumor Microenvironment Identifies Prognostic Gene Signature CD4/CD68/CSF1R in Osteosarcoma |
| title_full_unstemmed | Immune Landscape of the Tumor Microenvironment Identifies Prognostic Gene Signature CD4/CD68/CSF1R in Osteosarcoma |
| title_short | Immune Landscape of the Tumor Microenvironment Identifies Prognostic Gene Signature CD4/CD68/CSF1R in Osteosarcoma |
| title_sort | immune landscape of the tumor microenvironment identifies prognostic gene signature cd4 cd68 csf1r in osteosarcoma |
| topic | osteosarcoma tumor immune microenvironment prognostic gene signature tumor infiltrating immune cells tumor-associated macrophages tumor-infiltrating lymphocytes |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.01198/full |
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