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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\u2010based spatial transcriptomics on 10 clinical samples, we compared RR AITL with treatment\u2010responsive [non\u2010refractory\/recurrent event in 3\u2009years (NR)] cases to map the TME architecture. We identified a novel cluster of\n                    <jats:italic>NEIL3<\/jats:italic>\n                    + (Nei Like DNA Glycosylase 3) T\u2010follicular helper (Tfh) cells, which exhibited stem\u2010like characteristics at the transcriptional level, featuring self\u2010renewal 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\u2010mediated regulatory landscape. These findings provide comprehensive characterization of the TME ecosystem in AITL and reveal potential therapeutic targets for high\u2010risk RR AITL patients. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70035","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T10:39:09Z","timestamp":1771497549000},"page":"71-85","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Xenium\u2010based spatial transcriptomic analyses uncover prognosis\u2010associated heterogeneity in the tumor microenvironment (\n                    <scp>TME<\/scp>\n                    ) of angioimmunoblastic T\u2010cell lymphoma (\n                    <scp>AITL<\/scp>\n                    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