Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL)

Jun Du^1,†, Chen Qiu^2,†, Wei-Song Li^3,†, Bing Wang², Xin-Le Han⁴, Su-Wen Lin⁴, Xue-Hang Fu¹, Jian Hou^1,*, Zou-Fang Huang^5,*

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¹ Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127 Shanghai, China

² State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 300020 Tianjin, China

³ Department of Pathology, The First Affiliated Hospital of Gannan Medical University, 341000 Ganzhou, Jiangxi, China

⁴ Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, Guangdong, China

⁵ Ganzhou Key Laboratory of Hematology, Department of Hematology, The First Affiliated Hospital of Gannan Medical University, 341000 Ganzhou, Jiangxi, China

^*Correspondence: nfyyjsjj@126.com (Zou-Fang Huang); houjian@medmail.com.cn (Jian Hou)
^†These authors contributed equally.
Academic Editor: Graham Pawelec

Front. Biosci. (Landmark Ed) 2022, 27(9), 270; https://doi.org/10.31083/j.fbl2709270

Submitted: 5 April 2022 | Revised: 17 August 2022 | Accepted: 18 August 2022 | Published: 29 September 2022

This is an open access article under the CC BY 4.0 license.

Abstract

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.

Keywords

AITL

spatial transcriptomics

CCL17/CCL22-CCR4 axis

precision medicine

Funding

QD081/Youth Start-Up Fund for The First Affiliated Hospital of Gannan Medical University

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