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Xenium-based spatial transcriptomic analyses uncover prognosis-associated heterogeneity in the tumor microenvironment (TME) of angioimmunoblastic T-cell lymphoma (AITL)
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DOI：10.1002/path.70035.png)
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Abstract
En 中文
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.
Keywords:
Angioimmunoblastic T-cell lymphoma
spatial transcriptomic analyses
tumor microenvironment
prognosis
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