ArticleFrontiers in oncology2026
Multi-modal spatial glycomic analysis of lymphoid aggregates in prostate and pancreatic cancer tissues.
Article in Frontiers in oncology, 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
Introduction: Altered N-glycosylation plays a critical role in immune regulation, yet the spatial distribution of N-glycans within immune niches of immunologically "cold" tumors remain poorly defined. Here, we combine matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with highly multiplexed immunohistochemistry using photocleavable mass tags. This integrated workflow enables spatial mapping of N-glycosylation and immune markers within lymphoid aggregates (LAs) in prostate and pancreatic ductal adenocarcinoma tissues, two malignancies that respond poorly to immunotherapy. Given the role of N-glycosylation in immune regulation, spatially resolved N-glycan profiling may provide insight into molecular heterogeneity within lymphoid aggregates and their surrounding tumor microenvironment. Methods: To assess the relationship between N_glycosylation and immune markers, candidate LAs from tissue samples collected from patients with varying stages of prostate cancer, PCa (n=49) and pancreatic ductal adenocarcinoma, PDAC (n=26) were identified via histological stains prior to enzymatic release of N-glycans and MALDI-MSI. MALDI-IHC was used to target immune cell markers and extracellular matrix proteins. Results: In tissues with LAs, three N-glycan structural classes were identified when detectable: oligo-mannose, fucosylated tetra-antennary, and bisecting N-acetylglucosamine in fucosylated bi,- tri- and tetra- antennary structures, with some N-glycans common to both tumor types. LAs showed predominantly central CD20 and CD44 signal surrounded by CD3 signal localized along the tumor periphery. Conclusion: Our analysis revealed unique N-glycan patterns within and surrounding LAs, with variable profiles in distant regions, highlighting heterogeneity in LA-associated N-glycan profiles.
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