biostudies-literatureZhu MNatural Science Foundation of Jiangsu Province (Jiangsu Provincial Natural Science Foundation)National Natural Science Foundation of China (National Science Foundation of China)218https://www.ebi.ac.uk/biostudies/studies/S-EPMC11655871biostudies-literatureUnknown14(1)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 fromBlood cancer journalSingle-cell transcriptomic and spatial analysis reveal the immunosuppressive microenvironment in relapsed/refractory angioimmunoblastic T-cell lymphoma.PMC1165587191959113BK202105308237019332200590BK20211376821701858237289781972358Cao LYu LWu LLu XWang CRen YHu XLiu QShi WZhang LLin ZHuang RZhang RShi YLeng JJin HWang QFan LWu RWu WHuang BChen RLi JLu CXia PZhou WLi KLi NZhu MZhong SYao DCai YLv SfalseSingle-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⁺ T cell proportion and cytotoxicity decreased in RR-AITL TME, resulting from2024-01-01T00:00:00Z2024 Dec2025-04-04T21:45:33.252Z2025-04-04T21:45:33.252ZS-EPMC116558713969511810.1038/s41408-024-01199-0