Journal Article

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

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

2024

Overview

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 + 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.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: 13/1 / 13/51 / 38/39 / 45/91 / 631/67/327 / 631/80 / 692/699/1541/1990/291/1621/1916 / Biomedical and Life Sciences / Biomedicine / Cancer Research / Female / Gene Expression Regulation, Neoplastic / Hematology / Humans / Immunoblastic Lymphadenopathy - genetics / Immunoblastic Lymphadenopathy - immunology / Immunoblastic Lymphadenopathy - pathology / Lymphoma / Lymphoma, T-Cell - genetics / Lymphoma, T-Cell - immunology / Lymphoma, T-Cell - pathology / Male / Middle Aged / Neoplasm Recurrence, Local - genetics / Neoplasm Recurrence, Local - immunology / Neoplasm Recurrence, Local - pathology / Oncology / Single-Cell Analysis / Transcriptome / Tumor Microenvironment - immunology