CD8+ T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma
IntroductionMounting evidence has revealed that the interactions and dynamic alterations among immune cells are critical in shaping the tumor microenvironment and ultimately map onto heterogeneous clinical outcomes. Currently, the underlying clinical significance of immune cell evolutions remains la...
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Frontiers Media S.A.
2022-07-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.964190/full |
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| author | Long Liu Long Liu Long Liu Long Liu Zaoqu Liu Jie Gao Jie Gao Jie Gao Jie Gao Xudong Liu Xudong Liu Xudong Liu Xudong Liu Siyuan Weng Chunguang Guo Bowen Hu Bowen Hu Bowen Hu Bowen Hu Zhihui Wang Zhihui Wang Zhihui Wang Zhihui Wang Jiakai Zhang Jiakai Zhang Jiakai Zhang Jiakai Zhang Jihua Shi Jihua Shi Jihua Shi Jihua Shi Wenzhi Guo Wenzhi Guo Wenzhi Guo Wenzhi Guo Shuijun Zhang Shuijun Zhang Shuijun Zhang Shuijun Zhang |
| author_facet | Long Liu Long Liu Long Liu Long Liu Zaoqu Liu Jie Gao Jie Gao Jie Gao Jie Gao Xudong Liu Xudong Liu Xudong Liu Xudong Liu Siyuan Weng Chunguang Guo Bowen Hu Bowen Hu Bowen Hu Bowen Hu Zhihui Wang Zhihui Wang Zhihui Wang Zhihui Wang Jiakai Zhang Jiakai Zhang Jiakai Zhang Jiakai Zhang Jihua Shi Jihua Shi Jihua Shi Jihua Shi Wenzhi Guo Wenzhi Guo Wenzhi Guo Wenzhi Guo Shuijun Zhang Shuijun Zhang Shuijun Zhang Shuijun Zhang |
| author_sort | Long Liu |
| collection | DOAJ |
| description | IntroductionMounting evidence has revealed that the interactions and dynamic alterations among immune cells are critical in shaping the tumor microenvironment and ultimately map onto heterogeneous clinical outcomes. Currently, the underlying clinical significance of immune cell evolutions remains largely unexplored in hepatocellular carcinoma (HCC).MethodsA total of 3,817 immune cells and 1,750 HCC patients of 15 independent public datasets were retrieved. The Seurat and Monocle algorithms were used to depict T cell evolution, and nonnegative matrix factorization (NMF) was further applied to identify the molecular classification. Subsequently, the prognosis, biological characteristics, genomic variations, and immune landscape among distinct clusters were decoded. The clinical efficacy of multiple treatment approaches was further investigated.ResultsAccording to trajectory gene expression, three heterogeneous clusters with different clinical outcomes were identified. C2, with a more advanced pathological stage, presented the most dismal prognosis relative to C1 and C3. Eight independent external cohorts validated the robustness and reproducibility of the three clusters. Further explorations elucidated C1 to be characterized as lipid metabolic HCC, and C2 was referred to as cell-proliferative HCC, whereas C3 was defined as immune inflammatory HCC. Moreover, C2 also displayed the most conspicuous genomic instability, and C3 was deemed as “immune-hot”, having abundant immune cells and an elevated expression of immune checkpoints. The assessments of therapeutic intervention suggested that patients in C1 were suitable for transcatheter arterial chemoembolization treatment, and patients in C2 were sensitive to tyrosine kinase inhibitors, while patients in C3 were more responsive to immunotherapy. We also identified numerous underlying therapeutic agents, which might be conducive to clinical transformation in the future.ConclusionsOur study developed three clusters with distinct characteristics based on immune cell evolutions. For specifically stratified patients, we proposed individualized treatment strategies to improve the clinical outcomes and facilitate the clinical management. |
| first_indexed | 2024-04-12T08:05:14Z |
| format | Article |
| id | doaj.art-1038bb0cd6c44446802e03765a428846 |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T08:05:14Z |
| publishDate | 2022-07-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-1038bb0cd6c44446802e03765a4288462022-12-22T03:41:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.964190964190CD8+ T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinomaLong Liu0Long Liu1Long Liu2Long Liu3Zaoqu Liu4Jie Gao5Jie Gao6Jie Gao7Jie Gao8Xudong Liu9Xudong Liu10Xudong Liu11Xudong Liu12Siyuan Weng13Chunguang Guo14Bowen Hu15Bowen Hu16Bowen Hu17Bowen Hu18Zhihui Wang19Zhihui Wang20Zhihui Wang21Zhihui Wang22Jiakai Zhang23Jiakai Zhang24Jiakai Zhang25Jiakai Zhang26Jihua Shi27Jihua Shi28Jihua Shi29Jihua Shi30Wenzhi Guo31Wenzhi Guo32Wenzhi Guo33Wenzhi Guo34Shuijun Zhang35Shuijun Zhang36Shuijun Zhang37Shuijun Zhang38Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Research Centre for Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Diagnosis and Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering and Research Center for Diagnosis and Treatment of Hepatobiliary and Pancreatic Surgical Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Research Centre for Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Diagnosis and Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering and Research Center for Diagnosis and Treatment of Hepatobiliary and Pancreatic Surgical Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Research Centre for Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Diagnosis and Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering and Research Center for Diagnosis and Treatment of Hepatobiliary and Pancreatic Surgical Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Research Centre for Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Diagnosis and Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering and Research Center for Diagnosis and Treatment of Hepatobiliary and Pancreatic Surgical Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Research Centre for Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Diagnosis and Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering and Research Center for Diagnosis and Treatment of Hepatobiliary and Pancreatic Surgical Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Research Centre for Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Diagnosis and Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering and Research Center for Diagnosis and Treatment of Hepatobiliary and Pancreatic Surgical Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Research Centre for Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Diagnosis and Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering and Research Center for Diagnosis and Treatment of Hepatobiliary and Pancreatic Surgical Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Research Centre for Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Diagnosis and Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering and Research Center for Diagnosis and Treatment of Hepatobiliary and Pancreatic Surgical Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Research Centre for Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Diagnosis and Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering and Research Center for Diagnosis and Treatment of Hepatobiliary and Pancreatic Surgical Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaIntroductionMounting evidence has revealed that the interactions and dynamic alterations among immune cells are critical in shaping the tumor microenvironment and ultimately map onto heterogeneous clinical outcomes. Currently, the underlying clinical significance of immune cell evolutions remains largely unexplored in hepatocellular carcinoma (HCC).MethodsA total of 3,817 immune cells and 1,750 HCC patients of 15 independent public datasets were retrieved. The Seurat and Monocle algorithms were used to depict T cell evolution, and nonnegative matrix factorization (NMF) was further applied to identify the molecular classification. Subsequently, the prognosis, biological characteristics, genomic variations, and immune landscape among distinct clusters were decoded. The clinical efficacy of multiple treatment approaches was further investigated.ResultsAccording to trajectory gene expression, three heterogeneous clusters with different clinical outcomes were identified. C2, with a more advanced pathological stage, presented the most dismal prognosis relative to C1 and C3. Eight independent external cohorts validated the robustness and reproducibility of the three clusters. Further explorations elucidated C1 to be characterized as lipid metabolic HCC, and C2 was referred to as cell-proliferative HCC, whereas C3 was defined as immune inflammatory HCC. Moreover, C2 also displayed the most conspicuous genomic instability, and C3 was deemed as “immune-hot”, having abundant immune cells and an elevated expression of immune checkpoints. The assessments of therapeutic intervention suggested that patients in C1 were suitable for transcatheter arterial chemoembolization treatment, and patients in C2 were sensitive to tyrosine kinase inhibitors, while patients in C3 were more responsive to immunotherapy. We also identified numerous underlying therapeutic agents, which might be conducive to clinical transformation in the future.ConclusionsOur study developed three clusters with distinct characteristics based on immune cell evolutions. For specifically stratified patients, we proposed individualized treatment strategies to improve the clinical outcomes and facilitate the clinical management.https://www.frontiersin.org/articles/10.3389/fimmu.2022.964190/fullhepatocellular carcinomasingle-cell RNA-seqimmunotherapyheterogeneityprognosisclinical treatment |
| spellingShingle | Long Liu Long Liu Long Liu Long Liu Zaoqu Liu Jie Gao Jie Gao Jie Gao Jie Gao Xudong Liu Xudong Liu Xudong Liu Xudong Liu Siyuan Weng Chunguang Guo Bowen Hu Bowen Hu Bowen Hu Bowen Hu Zhihui Wang Zhihui Wang Zhihui Wang Zhihui Wang Jiakai Zhang Jiakai Zhang Jiakai Zhang Jiakai Zhang Jihua Shi Jihua Shi Jihua Shi Jihua Shi Wenzhi Guo Wenzhi Guo Wenzhi Guo Wenzhi Guo Shuijun Zhang Shuijun Zhang Shuijun Zhang Shuijun Zhang CD8+ T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma Frontiers in Immunology hepatocellular carcinoma single-cell RNA-seq immunotherapy heterogeneity prognosis clinical treatment |
| title | CD8+ T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma |
| title_full | CD8+ T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma |
| title_fullStr | CD8+ T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma |
| title_full_unstemmed | CD8+ T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma |
| title_short | CD8+ T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma |
| title_sort | cd8 t cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma |
| topic | hepatocellular carcinoma single-cell RNA-seq immunotherapy heterogeneity prognosis clinical treatment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.964190/full |
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