{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T13:32:38Z","timestamp":1793021558418,"version":"4.5.0"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Altered N-glycosylation plays a critical role in immune regulation, yet the spatial distribution of N-glycans within immune niches of immunologically \u201ccold\u201d 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1935795","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:38:54Z","timestamp":1790656734000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-modal spatial glycomic analysis of lymphoid aggregates in prostate and pancreatic cancer tissues"],"prefix":"10.3389","volume":"16","author":[{"given":"Kameisha V.","family":"Rashford","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Immunology and The Hollings Cancer Center, Medical University of South Carolina","place":["Charleston, SC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline G.","family":"Kittrell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology and The Hollings Cancer Center, Medical University of South Carolina","place":["Charleston, SC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsay E. 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