Single-cell transcriptomic and spatial analysis reveal the immunosuppressive microenvironment in relapsed/refractory angioimmunoblastic T-cell lymphoma

Angioimmunoblastic T-cell lymphoma (AITL) is a kind of aggressive T-cell lymphoma with significant enrichment of non-malignant tumor microenvironment (TME) cells. However, the complexity of TME in AITL progression is poorly understood. We performed single-cell RNA-Seq (scRNA-seq) and imaging mass cytometry (IMC) analysis to compare the cellular composition and spatial architecture between relapsed/refractory AITL (RR-AITL) and newly diagnosed AITL (ND-AITL). Our results showed that the malignant T follicular helper (Tfh) cells showed significantly increased proliferation driven by transcriptional activation of YY1 in RR-AITL, which is markedly associated with the poor prognosis of AITL patients. The CD8<sup>+</sup> T cell proportion and cytotoxicity decreased in RR-AITL TME, resulting from elevated expression of the inhibitory checkpoints such as PD-1, TIGIT, and CTLA4. Notably, the transcriptional pattern of B cells in RR-AITL showed an intermediate state of malignant transformation to B-cell-lymphoma, and contributed to immune evasion by highly expressing CD47 and PD-L1. Besides, compared to ND-AITL samples, myeloid-cells-centered spatial communities were more prevalent but showed reduced phagocytic activity and impaired antigen processing and presentation in RR-AITL TME. Furthermore, specific inhibitory ligand-receptor interactions, such as CLEC2D-KLRB1, CTLA4-CD86, and MIF-CD74, were exclusively identified in the RR-AITL TME. Our study provides a high-resolution characterization of the immunosuppression ecosystem and reveals the potential therapeutic targets for RR-AITL patients.

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Publication Details

Journal
Blood Cancer Journal
Published
2024-12-18
DOI
https://doi.org/10.1038/s41408-024-01199-0
Citations
15
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
6.37

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article

Single-cell transcriptomic and spatial analysis reveal the immunosuppressive microenvironment in relapsed/refractory angioimmunoblastic T-cell lymphoma

Lishen Zhang, Qianghu Wang, Xueying Lü, Diru Yao et al.
15 citations
Blood Cancer Journal
Lymphoma Diagnosis and Treatment
6.37
article

Single-cell transcriptomic and spatial analysis reveal the immunosuppressive microenvironment in relapsed/refractory angioimmunoblastic T-cell lymphoma

Lishen Zhang, Qianghu Wang, Xueying Lü, Diru Yao, Lei Fan, Shiyang Zhong, Bin Huang, Jia‐yan Leng, Xianglin Hu, Rongrong Wu, Ruohan Zhang, Wenyu Shi, Wanting Zhou, Quanzhong Liu, Renhong Huang, Kening Li, Chuanyang Lu, Wei Wu, Mengyan Zhu, Yun Cai, Ruize Chen, Sali Lv, Ning Li, Jianyong Li, Lei Cao, Zihan Lin, Liang Yu, Hui Jin, Lingxiang Wu, Peng Xia, Yimin Ren, Yuzhu Shi, Chunling Wang
article en
15 citations

Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is a kind of aggressive T-cell lymphoma with significant enrichment of non-malignant tumor microenvironment (TME) cells. However, the complexity of TME in AITL progression is poorly understood. We performed single-cell RNA-Seq (scRNA-seq) and imaging mass cytometry (IMC) analysis to compare the cellular composition and spatial architecture between relapsed/refractory AITL (RR-AITL) and newly diagnosed AITL (ND-AITL). Our results showed that the malignant T follicular helper (Tfh) cells showed significantly increased proliferation driven by transcriptional activation of YY1 in RR-AITL, which is markedly associated with the poor prognosis of AITL patients. The CD8<sup>+</sup> T cell proportion and cytotoxicity decreased in RR-AITL TME, resulting from elevated expression of the inhibitory checkpoints such as PD-1, TIGIT, and CTLA4. Notably, the transcriptional pattern of B cells in RR-AITL showed an intermediate state of malignant transformation to B-cell-lymphoma, and contributed to immune evasion by highly expressing CD47 and PD-L1. Besides, compared to ND-AITL samples, myeloid-cells-centered spatial communities were more prevalent but showed reduced phagocytic activity and impaired antigen processing and presentation in RR-AITL TME. Furthermore, specific inhibitory ligand-receptor interactions, such as CLEC2D-KLRB1, CTLA4-CD86, and MIF-CD74, were exclusively identified in the RR-AITL TME. Our study provides a high-resolution characterization of the immunosuppression ecosystem and reveals the potential therapeutic targets for RR-AITL patients.

Blood Cancer JournalVol. 14(1)
Jiangsu University (CN), Xuzhou Medical College (CN), Nantong University (CN), Affiliated Hospital of Nantong University (CN), Huaian First People’s Hospital (CN), Affiliated Hospital of Jiangsu University (CN), Second People’s Hospital of Huai’an (CN), Jiangsu Cancer Hospital (CN), Jiangsu Province Hospital (CN), Nanjing Medical University (CN)
National Natural Science Foundation of China, Government of Jiangsu Province, Natural Science Foundation of Jiangsu Province
Zero hunger
Openalex Percentile: Top 3%
Lymphoma Diagnosis and Treatment
6.37
DOIOpen Access PDFOpenAlex
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