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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Main Authors: Jun Du, Chen Qiu, Wei-Song Li, Bing Wang, Xin-Le Han, Su-Wen Lin, Xue-Hang Fu, Jian Hou, Zou-Fang Huang
Format: Article
Language:English
Published: IMR Press 2022-09-01
Series:Frontiers in Bioscience-Landmark
Subjects:
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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