Immunological Classification of Pancreatic Carcinomas to Identify Immune Index and Provide a Strategy for Patient Stratification
BackgroundCancer immunotherapy has produced significant positive clinical effects in a variety of tumor types. However, pancreatic ductal adenocarcinoma (PDAC) is widely considered to be a “cold” cancer with poor immunogenicity. Our aim is to determine the detailed immune features of PDAC to seek ne...
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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.2021.719105/full |
| _version_ | 1819005133634142208 |
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| author | Yi Chen Yi Chen Didi Chen Qiang Wang Yajing Xu Xiaowei Huang Felix Haglund Felix Haglund Huafang Su |
| author_facet | Yi Chen Yi Chen Didi Chen Qiang Wang Yajing Xu Xiaowei Huang Felix Haglund Felix Haglund Huafang Su |
| author_sort | Yi Chen |
| collection | DOAJ |
| description | BackgroundCancer immunotherapy has produced significant positive clinical effects in a variety of tumor types. However, pancreatic ductal adenocarcinoma (PDAC) is widely considered to be a “cold” cancer with poor immunogenicity. Our aim is to determine the detailed immune features of PDAC to seek new treatment strategies.MethodsThe immune cell abundance of PDAC patients was evaluated with the single-sample gene set enrichment analysis (ssGSEA) using 119 immune gene signatures. Based on these data, patients were classified into different immune subtypes (ISs) according to immune gene signatures. We analyzed their response patterns to immunotherapy in the datasets, then established an immune index to reflect the different degrees of immune infiltration through linear discriminant analysis (LDA). Finally, potential prognostic markers associated with the immune index were identified based on weighted correlation network analysis (WGCNA) that was functionally validated in vitro.ResultsThree ISs were identified in PDAC, of which IS3 had the best prognosis across all three cohorts. The different expressions of immune profiles among the three ISs indicated a distinct responsiveness to immunotherapies in PDAC subtypes. By calculating the immune index, we found that the IS3 represented higher immune infiltration, while IS1 represented lower immune infiltration. Among the investigated signatures, we identified ZNF185, FANCG, and CSTF2 as risk factors associated with immune index that could potentially facilitate diagnosis and could be therapeutic target markers in PDAC patients.ConclusionsOur findings identified immunologic subtypes of PDAC with distinct prognostic implications, which allowed us to establish an immune index to represent the immune infiltration in each subtype. These results show the importance of continuing investigation of immunotherapy and will allow clinical workers to personalized treatment more effectively in PDAC patients. |
| first_indexed | 2024-12-20T23:47:57Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T23:47:57Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f2fae199872a46a487a2df966b8518a72022-12-21T19:22:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.719105719105Immunological Classification of Pancreatic Carcinomas to Identify Immune Index and Provide a Strategy for Patient StratificationYi Chen0Yi Chen1Didi Chen2Qiang Wang3Yajing Xu4Xiaowei Huang5Felix Haglund6Felix Haglund7Huafang Su8Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenClinical Pathology and Cancer Diagnostics, Karolinska University Hospital Solna, Stockholm, SwedenDepartment of Radiation Oncology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, SwedenDepartment of Radiation Oncology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Radiation Oncology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenClinical Pathology and Cancer Diagnostics, Karolinska University Hospital Solna, Stockholm, SwedenDepartment of Radiation Oncology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaBackgroundCancer immunotherapy has produced significant positive clinical effects in a variety of tumor types. However, pancreatic ductal adenocarcinoma (PDAC) is widely considered to be a “cold” cancer with poor immunogenicity. Our aim is to determine the detailed immune features of PDAC to seek new treatment strategies.MethodsThe immune cell abundance of PDAC patients was evaluated with the single-sample gene set enrichment analysis (ssGSEA) using 119 immune gene signatures. Based on these data, patients were classified into different immune subtypes (ISs) according to immune gene signatures. We analyzed their response patterns to immunotherapy in the datasets, then established an immune index to reflect the different degrees of immune infiltration through linear discriminant analysis (LDA). Finally, potential prognostic markers associated with the immune index were identified based on weighted correlation network analysis (WGCNA) that was functionally validated in vitro.ResultsThree ISs were identified in PDAC, of which IS3 had the best prognosis across all three cohorts. The different expressions of immune profiles among the three ISs indicated a distinct responsiveness to immunotherapies in PDAC subtypes. By calculating the immune index, we found that the IS3 represented higher immune infiltration, while IS1 represented lower immune infiltration. Among the investigated signatures, we identified ZNF185, FANCG, and CSTF2 as risk factors associated with immune index that could potentially facilitate diagnosis and could be therapeutic target markers in PDAC patients.ConclusionsOur findings identified immunologic subtypes of PDAC with distinct prognostic implications, which allowed us to establish an immune index to represent the immune infiltration in each subtype. These results show the importance of continuing investigation of immunotherapy and will allow clinical workers to personalized treatment more effectively in PDAC patients.https://www.frontiersin.org/articles/10.3389/fimmu.2021.719105/fullpancreatic ductal adenocarcinoma (PDAC)immune characteristicsimmune subtypesimmune indeximmunotherapy |
| spellingShingle | Yi Chen Yi Chen Didi Chen Qiang Wang Yajing Xu Xiaowei Huang Felix Haglund Felix Haglund Huafang Su Immunological Classification of Pancreatic Carcinomas to Identify Immune Index and Provide a Strategy for Patient Stratification Frontiers in Immunology pancreatic ductal adenocarcinoma (PDAC) immune characteristics immune subtypes immune index immunotherapy |
| title | Immunological Classification of Pancreatic Carcinomas to Identify Immune Index and Provide a Strategy for Patient Stratification |
| title_full | Immunological Classification of Pancreatic Carcinomas to Identify Immune Index and Provide a Strategy for Patient Stratification |
| title_fullStr | Immunological Classification of Pancreatic Carcinomas to Identify Immune Index and Provide a Strategy for Patient Stratification |
| title_full_unstemmed | Immunological Classification of Pancreatic Carcinomas to Identify Immune Index and Provide a Strategy for Patient Stratification |
| title_short | Immunological Classification of Pancreatic Carcinomas to Identify Immune Index and Provide a Strategy for Patient Stratification |
| title_sort | immunological classification of pancreatic carcinomas to identify immune index and provide a strategy for patient stratification |
| topic | pancreatic ductal adenocarcinoma (PDAC) immune characteristics immune subtypes immune index immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.719105/full |
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