Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL)
Background: T cell lymphoma is a complex and highly aggressive clinicopathological entity with a poor outcome. The angioimmunoblastic T-cell lymphoma (AITL) tumor immune microenvironment is poorly investigated. Methods: Here, to the best of our knowledge, spatial transcriptomics was applied for the...
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IMR Press
2022-09-01
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Series: | Frontiers in Bioscience-Landmark |
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Online Access: | https://www.imrpress.com/journal/FBL/27/9/10.31083/j.fbl2709270 |
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author | Jun Du Chen Qiu Wei-Song Li Bing Wang Xin-Le Han Su-Wen Lin Xue-Hang Fu Jian Hou Zou-Fang Huang |
author_facet | Jun Du Chen Qiu Wei-Song Li Bing Wang Xin-Le Han Su-Wen Lin Xue-Hang Fu Jian Hou Zou-Fang Huang |
author_sort | Jun Du |
collection | DOAJ |
description | Background: T cell lymphoma is a complex and highly aggressive clinicopathological entity with a poor outcome. The angioimmunoblastic T-cell lymphoma (AITL) tumor immune microenvironment is poorly investigated. Methods: Here, to the best of our knowledge, spatial transcriptomics was applied for the first time to study AITL. Results: Using this method, we observed that AITL was surrounded by cells bearing immune-suppressive markers. CCL17 and CCL22, the dominant ligands for CCR4, were up-regulated, while the expression of natural killer (NK) cell and CD8+ cytotoxic T lymphocyte (CTL) markers decreased. Colocalization of Treg cells with the CD4+ TFH-GC region was also deduced from the bioinformatic analysis. The results obtained with spatial transcriptomics confirm that AITL has a suppressive immune environment. Chemotherapy based on the CHOP regimen (cyclophosphamide, doxorubicin, vincristine plus prednisone) induced complete remission (CR) in this AITL patient. However, the duration of remission (DoR) remains a concern. Conclusions: This study demonstrates that AITL has an immune suppressive environment and suggests that anti-CCR4 therapy could be a promising treatment for this lethal disease. |
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spelling | doaj.art-6e13b647ed4747809196e0f1513eeeed2022-12-22T02:24:49ZengIMR PressFrontiers in Bioscience-Landmark2768-67012022-09-0127927010.31083/j.fbl2709270S2768-6701(22)00623-2Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL)Jun Du0Chen Qiu1Wei-Song Li2Bing Wang3Xin-Le Han4Su-Wen Lin5Xue-Hang Fu6Jian Hou7Zou-Fang Huang8Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127 Shanghai, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 300020 Tianjin, ChinaDepartment of Pathology, The First Affiliated Hospital of Gannan Medical University, 341000 Ganzhou, Jiangxi, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 300020 Tianjin, ChinaBiomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, Guangdong, ChinaBiomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, Guangdong, ChinaDepartment of Hematology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127 Shanghai, ChinaDepartment of Hematology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127 Shanghai, ChinaGanzhou Key Laboratory of Hematology, Department of Hematology, The First Affiliated Hospital of Gannan Medical University, 341000 Ganzhou, Jiangxi, ChinaBackground: T cell lymphoma is a complex and highly aggressive clinicopathological entity with a poor outcome. The angioimmunoblastic T-cell lymphoma (AITL) tumor immune microenvironment is poorly investigated. Methods: Here, to the best of our knowledge, spatial transcriptomics was applied for the first time to study AITL. Results: Using this method, we observed that AITL was surrounded by cells bearing immune-suppressive markers. CCL17 and CCL22, the dominant ligands for CCR4, were up-regulated, while the expression of natural killer (NK) cell and CD8+ cytotoxic T lymphocyte (CTL) markers decreased. Colocalization of Treg cells with the CD4+ TFH-GC region was also deduced from the bioinformatic analysis. The results obtained with spatial transcriptomics confirm that AITL has a suppressive immune environment. Chemotherapy based on the CHOP regimen (cyclophosphamide, doxorubicin, vincristine plus prednisone) induced complete remission (CR) in this AITL patient. However, the duration of remission (DoR) remains a concern. Conclusions: This study demonstrates that AITL has an immune suppressive environment and suggests that anti-CCR4 therapy could be a promising treatment for this lethal disease.https://www.imrpress.com/journal/FBL/27/9/10.31083/j.fbl2709270aitlspatial transcriptomicsccl17/ccl22-ccr4 axisprecision medicine |
spellingShingle | Jun Du Chen Qiu Wei-Song Li Bing Wang Xin-Le Han Su-Wen Lin Xue-Hang Fu Jian Hou Zou-Fang Huang Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL) Frontiers in Bioscience-Landmark aitl spatial transcriptomics ccl17/ccl22-ccr4 axis precision medicine |
title | Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL) |
title_full | Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL) |
title_fullStr | Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL) |
title_full_unstemmed | Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL) |
title_short | Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL) |
title_sort | spatial transcriptomics analysis reveals that ccl17 and ccl22 are robust indicators of a suppressive immune environment in angioimmunoblastic t cell lymphoma aitl |
topic | aitl spatial transcriptomics ccl17/ccl22-ccr4 axis precision medicine |
url | https://www.imrpress.com/journal/FBL/27/9/10.31083/j.fbl2709270 |
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