Xenium‐based spatial transcriptomic analyses uncover prognosis‐associated heterogeneity in the tumor microenvironment ( TME ) of angioimmunoblastic T‐cell lymphoma ( AITL )

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Autori principali: Jiyan Dong, Xiaoyue Xiao, Lin Nong, Xuemin Xue, Long Wang, Xujie Sun, Kang Jiang, Xiaoli Feng
Natura: Artículo Open Access
Pubblicazione: Wiley 2026
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author Jiyan Dong
Xiaoyue Xiao
Lin Nong
Xuemin Xue
Long Wang
Xujie Sun
Kang Jiang
Xiaoli Feng
author_facet Jiyan Dong
Xiaoyue Xiao
Lin Nong
Xuemin Xue
Long Wang
Xujie Sun
Kang Jiang
Xiaoli Feng
Jiyan Dong
Xiaoyue Xiao
Lin Nong
Xuemin Xue
Long Wang
Xujie Sun
Kang Jiang
Xiaoli Feng
collection Wiley Open Access
contents Xenium‐based spatial transcriptomic analyses uncover prognosis‐associated heterogeneity in the tumor microenvironment ( TME ) of angioimmunoblastic T‐cell lymphoma ( AITL ) Jiyan Dong Xiaoyue Xiao Lin Nong Xuemin Xue Long Wang Xujie Sun Kang Jiang Xiaoli Feng The Journal of Pathology Abstract Angioimmunoblastic T‐cell lymphoma (AITL) exemplifies a neoplasm characterized by prominent inflammatory infiltration and robust immune responses in the tumor microenvironment (TME). The pathophysiology of refractory/recurrent (RR) AITL remains poorly understood due to profound intratumoral heterogeneity and complex TME features, contributing to limited therapeutic efficacy. Using Xenium‐based spatial transcriptomics on 10 clinical samples, we compared RR AITL with treatment‐responsive [non‐refractory/recurrent event in 3 years (NR)] cases to map the TME architecture. We identified a novel cluster of NEIL3 + (Nei Like DNA Glycosylase 3) T‐follicular helper (Tfh) cells, which exhibited stem‐like characteristics at the transcriptional level, featuring self‐renewal and multilineage differentiation capacity, and were highly enriched in RR tumors. Furthermore, we found major differences in immune cell organization between NR and RR microenvironments: RR cases were dominated by B cells primed for adaptive immunity and myeloid cells driving angiogenesis, whereas NR cases exhibited a chemokine‐mediated regulatory landscape. These findings provide comprehensive characterization of the TME ecosystem in AITL and reveal potential therapeutic targets for high‐risk RR AITL patients. © 2026 The Pathological Society of Great Britain and Ireland. 10.1002/path.70035 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/path.70035
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spellingShingle Xenium‐based spatial transcriptomic analyses uncover prognosis‐associated heterogeneity in the tumor microenvironment ( TME ) of angioimmunoblastic T‐cell lymphoma ( AITL )
Jiyan Dong
Xiaoyue Xiao
Lin Nong
Xuemin Xue
Long Wang
Xujie Sun
Kang Jiang
Xiaoli Feng
The Journal of Pathology
Xenium‐based spatial transcriptomic analyses uncover prognosis‐associated heterogeneity in the tumor microenvironment ( TME ) of angioimmunoblastic T‐cell lymphoma ( AITL ) Jiyan Dong Xiaoyue Xiao Lin Nong Xuemin Xue Long Wang Xujie Sun Kang Jiang Xiaoli Feng The Journal of Pathology Abstract Angioimmunoblastic T‐cell lymphoma (AITL) exemplifies a neoplasm characterized by prominent inflammatory infiltration and robust immune responses in the tumor microenvironment (TME). The pathophysiology of refractory/recurrent (RR) AITL remains poorly understood due to profound intratumoral heterogeneity and complex TME features, contributing to limited therapeutic efficacy. Using Xenium‐based spatial transcriptomics on 10 clinical samples, we compared RR AITL with treatment‐responsive [non‐refractory/recurrent event in 3 years (NR)] cases to map the TME architecture. We identified a novel cluster of NEIL3 + (Nei Like DNA Glycosylase 3) T‐follicular helper (Tfh) cells, which exhibited stem‐like characteristics at the transcriptional level, featuring self‐renewal and multilineage differentiation capacity, and were highly enriched in RR tumors. Furthermore, we found major differences in immune cell organization between NR and RR microenvironments: RR cases were dominated by B cells primed for adaptive immunity and myeloid cells driving angiogenesis, whereas NR cases exhibited a chemokine‐mediated regulatory landscape. These findings provide comprehensive characterization of the TME ecosystem in AITL and reveal potential therapeutic targets for high‐risk RR AITL patients. © 2026 The Pathological Society of Great Britain and Ireland. 10.1002/path.70035 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Xenium‐based spatial transcriptomic analyses uncover prognosis‐associated heterogeneity in the tumor microenvironment ( TME ) of angioimmunoblastic T‐cell lymphoma ( AITL )
topic The Journal of Pathology
url https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.70035