ArticleActa neuropathologica communications2026
Immune landscape characterization of neurofibromas with atypical features in Neurofibromatosis1 reveals PD-1 and the Tim-3/Galectin-9 pathway as potential therapeutic targets.
Article in Acta neuropathologica communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Neurofibromatosis type 1 (NF1) is a genetic disorder that predisposes individuals to the development of plexiform neurofibromas (pNF), benign tumors of the nerve sheath that can progress to malignant peripheral nerve sheath tumors (MPNST). Some pNFs exhibit atypical characteristics, particularly atypical neurofibromatous neoplasms of uncertain biological potential (ANNUBP), which meet recently defined criteria. These are pNFs with concerning histological and/or molecular features and uncertain behavior, leading to their consideration as potential precursors of MPNSTs. In this study, we characterized the immune landscape of a series of atypical neurofibromas (exhibiting increased cellularity or atypical cells) and ANNUBPs (ANF/ANNUBP) compared to cutaneous neurofibromas (cNF), pNFs, and MPNSTs, all from patients with NF1, using immunohistochemistry and single-cell RNA sequencing (scRNA-seq). Our findings revealed that ANF/ANNUBPs are heavily infiltrated with CD3+ T-lymphocytes and CD163+ macrophages. Transcriptomic profiling using the NanoString technology demonstrated that ANF/ANNUBPs exhibit a distinct immune signature compared to both pNFs and MPNSTs. This includes overexpression of two inhibitory immune checkpoints (ICs): HAVCR2 (encoding the IC receptor Tim-3) and its primary ligand Galectin-9 (Gal9). Subsequent analyses of scRNA datasets corroborated these findings with Prss56
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