The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma
BackgroundMAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response.MethodsSix metas...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.785526/full |
| _version_ | 1818968561430822912 |
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| author | Ting Ye Jie-Ying Zhang Xin-Yi Liu Yu-Han Zhou Si-Yue Yuan Meng-Mei Yang Wen-Zhuan Xie Chan Gao Yao-Xu Chen Meng-Li Huang Cheng-Zhi Ye Jing Chen |
| author_facet | Ting Ye Jie-Ying Zhang Xin-Yi Liu Yu-Han Zhou Si-Yue Yuan Meng-Mei Yang Wen-Zhuan Xie Chan Gao Yao-Xu Chen Meng-Li Huang Cheng-Zhi Ye Jing Chen |
| author_sort | Ting Ye |
| collection | DOAJ |
| description | BackgroundMAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response.MethodsSix metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation.ResultsCompared to patients with wild-type MAP2K1/2, those with MAP2K1/2 mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between MAP2K1/2 mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with MAP2K1/2 mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with MAP2K mutation was enriched in CD8+ T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with MAP2K1/2 mutations from anti-CTLA-4 treatment.ConclusionsMAP2K1/2 mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with MAP2K1/2-mutated melanoma. |
| first_indexed | 2024-12-20T14:06:39Z |
| format | Article |
| id | doaj.art-50187cd1ca0944e19194a0cfe0e95104 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T14:06:39Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-50187cd1ca0944e19194a0cfe0e951042022-12-21T19:38:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.785526785526The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in MelanomaTing Ye0Jie-Ying Zhang1Xin-Yi Liu2Yu-Han Zhou3Si-Yue Yuan4Meng-Mei Yang5Wen-Zhuan Xie6Chan Gao7Yao-Xu Chen8Meng-Li Huang9Cheng-Zhi Ye10Jing Chen11Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaThe Medical Department, 3D Medicines Inc., Shanghai, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaThe Medical Department, 3D Medicines Inc., Shanghai, ChinaThe Medical Department, 3D Medicines Inc., Shanghai, ChinaThe Medical Department, 3D Medicines Inc., Shanghai, ChinaThe Medical Department, 3D Medicines Inc., Shanghai, ChinaThe Medical Department, 3D Medicines Inc., Shanghai, ChinaDepartment of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBackgroundMAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response.MethodsSix metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation.ResultsCompared to patients with wild-type MAP2K1/2, those with MAP2K1/2 mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between MAP2K1/2 mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with MAP2K1/2 mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with MAP2K mutation was enriched in CD8+ T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with MAP2K1/2 mutations from anti-CTLA-4 treatment.ConclusionsMAP2K1/2 mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with MAP2K1/2-mutated melanoma.https://www.frontiersin.org/articles/10.3389/fimmu.2021.785526/fullmelanomaCTLA-4 blockadePD-1 blockadeMAPK pathwayimmunotherapy |
| spellingShingle | Ting Ye Jie-Ying Zhang Xin-Yi Liu Yu-Han Zhou Si-Yue Yuan Meng-Mei Yang Wen-Zhuan Xie Chan Gao Yao-Xu Chen Meng-Li Huang Cheng-Zhi Ye Jing Chen The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma Frontiers in Immunology melanoma CTLA-4 blockade PD-1 blockade MAPK pathway immunotherapy |
| title | The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma |
| title_full | The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma |
| title_fullStr | The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma |
| title_full_unstemmed | The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma |
| title_short | The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma |
| title_sort | predictive value of map2k1 2 mutations on efficiency of immunotherapy in melanoma |
| topic | melanoma CTLA-4 blockade PD-1 blockade MAPK pathway immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.785526/full |
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