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We performed immune profiling in SD- and LD-iCCA to identify novel biomarker candidates for personalized medicine.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Retrospectively, 19 iCCA patients with either SD-iCCA (n\u2009=\u200910, median age, 63.1\u00a0years (45\u201386); men, 4) or LD-iCCA (n\u2009=\u20099, median age, 69.7\u00a0years (62\u201385); men, 5)) were included. All patients were diagnosed and histologically confirmed between 04\/2009 and 01\/2021. Tumor tissue samples were processed for differential expression profiling using NanoString nCounter\u00ae PanCancer Immune Profiling Panel.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>With the exception of complement signatures, immune-related pathways were broadly downregulated in SD-iCCA vs. LD-iCCA. A total of 20 immune-related genes were strongly downregulated in SD-iCCA with DMBT1 (log2fc\u2009=\u2009-5.39, <jats:italic>p<\/jats:italic>\u2009=\u20090.01) and CEACAM6 (log2fc\u2009=\u2009-6.38, <jats:italic>p<\/jats:italic>\u2009=\u20090.01) showing the strongest downregulation. Among 7 strongly (log2fc\u2009&gt;\u20092, <jats:italic>p<\/jats:italic>\u2009\u2264\u20090.02) upregulated genes, CRP (log2fc\u2009=\u20095.06, <jats:italic>p<\/jats:italic>\u2009=\u20090.02) ranked first, and four others were associated with complement (C5, C4BPA, C8A, C8B). Total tumor-infiltrating lymphocytes (TIL) signature was decreased in SD-iCCA with elevated ratios of exhausted-CD8\/TILs, NK\/TILs, and cytotoxic cells\/TILs while having decreased ratios of B-cells\/TILs, mast cells\/TILs and dendritic cells\/TILs. The immune profiling signatures in SD-iCCA revealed downregulation in chemokine signaling pathways inclulding JAK2\/3 and ERK1\/2 as well as nearly all cytokine-cytokine receptor interaction pathways with the exception of the CXCL1\/CXCR1-axis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Immune patterns differed in SD-iCCA versus LD-iCCA. We identified potential biomarker candidate genes, including CRP, CEACAM6, DMBT1, and various complement factors that could be explored for augmented diagnostics and treatment decision-making.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-024-05888-y","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T03:11:21Z","timestamp":1721617881000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Small duct and large duct type intrahepatic cholangiocarcinoma reveal distinct patterns of immune signatures"],"prefix":"10.1007","volume":"150","author":[{"given":"Simon","family":"Bernatz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falko","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Bein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Bankov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scherwin","family":"Mahmoudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon D.","family":"Gr\u00fcnewald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitali","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Stehle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas A.","family":"Schnitzbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-9624","authenticated-orcid":false,"given":"Dirk","family":"Walter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-9910","authenticated-orcid":false,"given":"Fabian","family":"Finkelmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0845-6833","authenticated-orcid":false,"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Vogl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Wild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2378-1455","authenticated-orcid":false,"given":"Maximilian N.","family":"Kinzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"5888_CR1","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1002\/jhbp.154","volume":"22","author":"S Aishima","year":"2015","unstructured":"Aishima S, Oda Y (2015) Pathogenesis and classification of intrahepatic cholangiocarcinoma: different characters of perihilar large duct type versus peripheral small duct type. 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F. has received travel support from Ipsen, Abbvie, Astrazeneca and speaker\u2019s fees from AbbVie, MSD, Ipsen, Astra. S.Z. has received speaker fees and\/or honoraria for consultancy from Abbvie, BioMarin, Gilead, Intercept, Janssen, Madrigal, MSD\/Merck, NovoNordisk, SoBi and Theratechnologies. P.J.W. has received consulting fees and honoraria for lectures by Bayer, Janssen-Cilag, Novartis, Roche, MSD, Astellas Pharma, Bristol-Myers Squibb, Thermo Fisher Scientific, Molecular Health, Guardant Health, Sophia Genetics, Qiagen, Eli Lilly, Myriad, Hedera Dx, and Astra Zeneca; research support was provided by Astra Zeneca. The authors declare that there is no relationship relevant to the manuscripts\u2019 subject. All other authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"The study was performed in accordance with the Declaration of Helsinki. The study protocol was approved by the local ethics committee of the University of Frankfurt (project-number: SGI-1\u20132021, SGI-3\u20132021).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Patients provided informed written consent and patient data was provided after approval by the local ethics committee.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}],"article-number":"357"}}