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Pancreatic cancer-associated fibroblasts modulate macrophage differentiation via sialic acid-Siglec interactions | Scholarly Publications
<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML+RDFa 1.0//EN" "http://www.w3.org/MarkUp/DTD/xhtml-rdfa-1.dtd"> <html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" version="XHTML+RDFa 1.0" dir="ltr" xmlns:content="http://purl.org/rss/1.0/modules/content/" xmlns:dc="http://purl.org/dc/terms/" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:og="http://ogp.me/ns#" xmlns:rdfs="http://www.w3.org/2000/01/rdf-schema#" xmlns:sioc="http://rdfs.org/sioc/ns#" xmlns:sioct="http://rdfs.org/sioc/types#" xmlns:skos="http://www.w3.org/2004/02/skos/core#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#"> <head profile="http://www.w3.org/1999/xhtml/vocab"> <meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <meta name="Generator" content="Drupal 7 (http://drupal.org)" /> <meta name="citation_title" content="Pancreatic cancer-associated fibroblasts modulate macrophage differentiation via sialic acid-Siglec interactions" /> <meta name="citation_publication_date" content="2024-04-09" /> <meta name="citation_book_title" content="Communications Biology" /> <meta name="citation_journal_title" content="Communications Biology" /> <meta name="citation_volume" content="7" /> <meta name="citation_issue" content="1" /> <meta name="citation_doi" content="doi:10.1038/s42003-024-06087-8" /> <meta name="citation_public_url" content="https://hdl.handle.net/1887/4195909" /> <meta name="citation_language" content="en" /> <meta name="citation_abstract_html_url" content="https://scholarlypublications.universiteitleiden.nl/handle/1887/4195909/" /> <link rel="shortcut icon" href="https://scholarlypublications.universiteitleiden.nl/sites/scholarlypublications.universiteitleiden.nl/files/favicon_0.ico" type="image/vnd.microsoft.icon" /> <meta name="viewport" content="width=device-width, initial-scale=1" /> <meta name="citation_author" content="Boelaars, K." /> <meta name="citation_author" content="Rodriguez, E." /> <meta name="citation_author" content="Huinen, Z.R." /> <meta name="citation_author" content="Liu, C." /> <meta name="citation_author" content="Wang, D." /> <meta name="citation_author" content="Springer, B.O." /> <meta name="citation_author" content="Olesek, K." /> <meta name="citation_author" content="Goossens-Kruijssen, L." /> <meta name="citation_author" content="Ee, T. van" /> <meta name="citation_author" content="Lindijer, D." /> <meta name="citation_author" content="Tak, W." /> <meta name="citation_author" content="Haas, A. de" /> <meta name="citation_author" content="Wehry, L." /> <meta name="citation_author" content="Nugteren-Boogaard, J.P." /> <meta name="citation_author" content="Mikula, A." /> <meta name="citation_author" content="Winde, C.M. de" /> <meta name="citation_author" content="Mebius, R.E." /> <meta name="citation_author" content="Tuveson, D.A." /> <meta name="citation_author" content="Giovannetti, E." /> <meta name="citation_author" content="Bijlsma, M.F." /> <meta name="citation_author" content="Wuhrer, M." /> <meta name="citation_author" content="Vliet, S.J. van" /> <meta name="citation_author" content="Kooyk, Y. van" /> <meta name="citation_abstract" content=" Despite recent advances in cancer immunotherapy, pancreatic ductal adenocarcinoma (PDAC) remains unresponsive due to an immunosuppressive tumor microenvironment, which is characterized by the abundance of cancer-associated fibroblasts (CAFs). Once identified, CAF-mediated immune inhibitory mechanisms could be exploited for cancer immunotherapy. Siglec receptors are increasingly recognized as immune checkpoints, and their ligands, sialic acids, are known to be overexpressed by cancer cells. Here, we unveil a previously unrecognized role of sialic acid-containing glycans on PDAC CAFs as crucial modulators of myeloid cells. Using multiplex immunohistochemistry and transcriptomics, we show that PDAC stroma is enriched in sialic acid-containing glycans compared to tumor cells and normal fibroblasts, and characterized by ST3GAL4 expression. We demonstrate that sialic acids on CAF cell lines serve as ligands for Siglec-7, -9, -10 and -15, distinct from the ligands on tumor cells, and that these receptors are found on myeloid cells in the stroma of PDAC biopsies. Furthermore, we show that CAFs drive the differentiation of monocytes to immunosuppressive tumor-associated macrophages in vitro, and that CAF sialylation plays a dominant role in this process compared to tumor cell sialylation. Collectively, our findings unravel sialic acids as a mechanism of CAF-mediated immunomodulation, which may provide targets for immunotherapy in PDAC. 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fibroblasts modulate macrophage differentiation via sialic acid-Siglec interactions" /> </div> </div> <section class="dc-metadata islandora islandora-metadata"> <!-- Metadata --> <div class="fieldset-wrapper"> <dd class="first author"> <span class="name"> <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ABoelaars%2C%5C%20K.">Boelaars, K.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ARodriguez%2C%5C%20E.">Rodriguez, E.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AHuinen%2C%5C%20Z.R.">Huinen, Z.R.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ALiu%2C%5C%20C.">Liu, C.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AWang%2C%5C%20D.">Wang, D.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ASpringer%2C%5C%20B.O.">Springer, B.O.</a>; ... ; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AKooyk%2C%5C%20Y.%5C%20van">Kooyk, Y. van</a> </span> <span class="year"> (2024) </span> </dd> <dd class="title"> <h3> Pancreatic cancer-associated fibroblasts modulate macrophage differentiation via sialic acid-Siglec interactions </h3> </dd> <dd class="genre"> <a href="/search?type=dismax&f%5B0%5D=mods_genre_authority_local_ms%3AArticle%5C%20%5C/%5C%20Letter%5C%20to%5C%20editor">Article / Letter to editor</a> </dd> <dd class="abstract"> <span class="toggle-wrapper"><span> Despite recent advances in cancer immunotherapy, pancreatic ductal adenocarcinoma (PDAC) remains unresponsive due to an immunosuppressive tumor microenvironment, which is characterized by the abundance of cancer-associated fibroblasts (CAFs). Once identified, CAF-mediated immune inhibitory mechanisms could be exploited for cancer immunotherapy. Siglec receptors are increasingly recognized as immune checkpoints, and their ligands, sialic acids, are known to be overexpressed by cancer cells. Here, we unveil a previously unrecognized role of sialic acid-containing glycans on PDAC CAFs as crucial modulators of myeloid cells. Using multiplex immunohistochemistry and transcriptomics, we show that PDAC stroma is enriched in sialic acid-containing glycans compared to tumor cells and normal fibroblasts, and characterized by ST3GAL4 expression. We demonstrate that sialic acids on CAF cell lines serve as ligands for Siglec-7, -9, -10 and -15, distinct from the ligands on tumor cells, and...<a href='#' class='toggler'>Show more</a></span><span> Despite recent advances in cancer immunotherapy, pancreatic ductal adenocarcinoma (PDAC) remains unresponsive due to an immunosuppressive tumor microenvironment, which is characterized by the abundance of cancer-associated fibroblasts (CAFs). Once identified, CAF-mediated immune inhibitory mechanisms could be exploited for cancer immunotherapy. Siglec receptors are increasingly recognized as immune checkpoints, and their ligands, sialic acids, are known to be overexpressed by cancer cells. Here, we unveil a previously unrecognized role of sialic acid-containing glycans on PDAC CAFs as crucial modulators of myeloid cells. Using multiplex immunohistochemistry and transcriptomics, we show that PDAC stroma is enriched in sialic acid-containing glycans compared to tumor cells and normal fibroblasts, and characterized by ST3GAL4 expression. We demonstrate that sialic acids on CAF cell lines serve as ligands for Siglec-7, -9, -10 and -15, distinct from the ligands on tumor cells, and that these receptors are found on myeloid cells in the stroma of PDAC biopsies. Furthermore, we show that CAFs drive the differentiation of monocytes to immunosuppressive tumor-associated macrophages in vitro, and that CAF sialylation plays a dominant role in this process compared to tumor cell sialylation. Collectively, our findings unravel sialic acids as a mechanism of CAF-mediated immunomodulation, which may provide targets for immunotherapy in PDAC. <br /><a href='#' class='toggler'>Show less</a></span></span> </dd> <dl title="All authors" class="mods_name_AuthorRole_namePart_custom_ms"> <dt>All authors</dt> <dd><a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ABoelaars%2C%5C%20K.">Boelaars, K.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ARodriguez%2C%5C%20E.">Rodriguez, E.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AHuinen%2C%5C%20Z.R.">Huinen, Z.R.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ALiu%2C%5C%20C.">Liu, C.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AWang%2C%5C%20D.">Wang, D.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ASpringer%2C%5C%20B.O.">Springer, B.O.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AOlesek%2C%5C%20K.">Olesek, K.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AGoossens%5C-Kruijssen%2C%5C%20L.">Goossens-Kruijssen, L.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AEe%2C%5C%20T.%5C%20van">Ee, T. van</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ALindijer%2C%5C%20D.">Lindijer, D.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ATak%2C%5C%20W.">Tak, W.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AHaas%2C%5C%20A.%5C%20de">Haas, A. de</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AWehry%2C%5C%20L.">Wehry, L.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ANugteren%5C-Boogaard%2C%5C%20J.P.">Nugteren-Boogaard, J.P.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AMikula%2C%5C%20A.">Mikula, A.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AWinde%2C%5C%20C.M.%5C%20de">Winde, C.M. de</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AMebius%2C%5C%20R.E.">Mebius, R.E.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ATuveson%2C%5C%20D.A.">Tuveson, D.A.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AGiovannetti%2C%5C%20E.">Giovannetti, E.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3ABijlsma%2C%5C%20M.F.">Bijlsma, M.F.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AWuhrer%2C%5C%20M.">Wuhrer, M.</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AVliet%2C%5C%20S.J.%5C%20van">Vliet, S.J. van</a>; <a href="/search?type=dismax&f%5B0%5D=mods_name_AuthorRole_namePart_custom_ms%3AKooyk%2C%5C%20Y.%5C%20van">Kooyk, Y. van</a></dd> </dl> <dl title="Date" class="mods_originInfo_encoding_w3cdtf_keyDate_yes_dateIssued_ms"> <dt>Date</dt> <dd>2024-04-09</dd> </dl> <dl title="Journal" class="mods_relatedItem_host_titleInfo_title_ms"> <dt>Journal</dt> <dd> <a href="/search?type=dismax&f%5B0%5D=mods_relatedItem_host_titleInfo_title_ms%3ACommunications%5C%20Biology">Communications Biology</a> </dd> </dl> <dl title="Volume" class="mods_relatedItem_host_part_detail_volume_number_ms"> <dt>Volume</dt> <dd>7</dd> </dl> <dl title="Issue" class="mods_relatedItem_host_part_detail_issue_number_ms"> <dt>Issue</dt> <dd>1</dd> </dl> <dl title="DOI" class="mods_identifier_doi_ms"> <dt>DOI</dt> <dd> <a href="https://doi.org/doi:10.1038/s42003-024-06087-8" absolute="1" target="_blank">doi:10.1038/s42003-024-06087-8</a> </dd> </dl> <dl title="Link" class="mods_identifier_uri_ms"> <dt>Link</dt> <dd><a href="https://www.nature.com/articles/s42003-024-06087-8">https://www.nature.com/articles/s42003-024-06087-8</a></dd> </dl> </div> </section> </div> </div> </div> </section> </div> </div></div> <!-- /.section, /.dc-content --> </div> <!-- /.dc-centercontent --> </main> <!-- /#themain, /#main-wrapper --> <footer id="thefooter"><div class="dc-centercontent"> <div class="region region-footer"> <section class=""> <div id="block-block-3" class="block block-block"> <div class="content"> <p>©2020-2024 Leiden University<br /> A service provided by <a target="”_blank”" href="https://www.library.universiteitleiden.nl/">Leiden University Libraries</a></p> </div> </div> </section><section class=""> <div id="block-menu-menu-footer-menu" class="block block-menu"> <div class="content"> <ul class="menu"><li class="first leaf"><a href="https://www.library.universiteitleiden.nl/about-us/contact" class="first leaf" target="_blank">Contact</a></li><li class="leaf"><a href="/about" class="leaf">About us</a></li><li class="leaf"><a href="/added-last-2-weeks" class="leaf">Recently Added</a></li><li class="leaf"><a href="https://digitalcollections.universiteitleiden.nl/" class="leaf" target="_blank">Digital Collections</a></li><li class="last leaf"><a href="https://studenttheses.universiteitleiden.nl/" class="last leaf" target="_blank">Student Repository</a></li></ul> </div> </div> </section> </div> </div></footer> <!-- /.section, /#footer --> </div></div> <!-- /#page, /#page-wrapper --> </body> </html>