{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:12:39Z","timestamp":1793329959665,"version":"4.5.0"},"reference-count":79,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"unspecified","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Health Research Charities Ireland -Health Research Board","award":["HRCI-HRB-2024-018"],"award-info":[{"award-number":["HRCI-HRB-2024-018"]}]},{"DOI":"10.13039\/501100001593","name":"Irish Cancer Society","doi-asserted-by":"crossref","award":["CRS22WAL"],"award-info":[{"award-number":["CRS22WAL"]}],"id":[{"id":"10.13039\/501100001593","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science Foundation Ireland and the Engineering and Physical Sciences Research Council Centre for Doctoral Training in Engineered Tissues for Discovery, Industry and Medicine","award":["18\/EPSRC-CDT\/3583, EP\/S02347X\/1"],"award-info":[{"award-number":["18\/EPSRC-CDT\/3583, EP\/S02347X\/1"]}]},{"DOI":"10.13039\/501100001602","name":"Research Ireland","doi-asserted-by":"publisher","award":["15\/SIRG\/3456, 19\/FFP\/6446"],"award-info":[{"award-number":["15\/SIRG\/3456, 19\/FFP\/6446"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,9,15]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The immunosuppressive tumor microenvironment reduces immune response effectiveness in stromal-rich tumors, including consensus molecular subtype 4 colorectal cancer (CRC). Mesenchymal stromal cells (MSCs), precursors to cancer-associated fibroblasts (CAFs), promote cancer progression by suppressing anti-tumor immune responses. Hypersialylation of glycans on tumors engages Siglec receptors on immune cells, driving immune dysfunction, but its role in stromal-mediated suppression of innate immunity remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sialylation, Sialic acids and Siglec ligands were measured on CRC tissue, primary human normal-associated fibroblasts (NAFs), CAFs, and tumor-conditioned MSCs (MSC\n                      <jats:sup>TCS<\/jats:sup>\n                      ) using transcriptional profiles, immunohistochemistry and flow cytometry, respectively. The effect of stromal cell sialylation on macrophages and NK cells was assessed in\n                      <jats:italic>ex vivo<\/jats:italic>\n                      human primary stromal and immune cell co-cultures, and expression of Siglec-10 and immune cell phenotype markers and function was measured by flow cytometry and real-time imaging. Using an immunocompetent Balb\/c CT26 mouse model, we induced tumors with\/without conditioned stromal cells, with\/without pretreatment of stromal cells with sialyltransferase inhibitor (3FAX) or sialidase (E610). We assessed the effect of stromal cell sialylation on macrophages and NK cells in the tumor and secondary lymphoid tissues by flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Stromal cells, including CAFs, in CRC tumors are highly sialylated compared with epithelial cancer cells and are associated with high expression of the sialyltransferase\n                      <jats:italic>ST6GALNAC6<\/jats:italic>\n                      . Genetic knockdown of\n                      <jats:italic>ST6GALNAC6<\/jats:italic>\n                      reduced the expression of stromal cell Siglec-10 ligands in MSCs. CAFs and MSC\n                      <jats:sup>TCS<\/jats:sup>\n                      induced Siglec-10 on macrophages and NK cells and impaired macrophage phagocytosis and NK cell cytotoxicity. Sialidase treatment reduced Siglec-10 expression, restoring macrophage and NK cell antitumor functions.\n                      <jats:italic>In vivo<\/jats:italic>\n                      and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      , desialylation of stromal cells increased macrophage activation (CD11b\n                      <jats:sup>+<\/jats:sup>\n                      CD80\n                      <jats:sup>+<\/jats:sup>\n                      ) and reduced immunosuppressive marker expression (CD206, PD-L1, Siglec-G) in lymphoid tissues, indicating sustained systemic anti-tumor immunity. Intratumoral NK cells exhibited high Siglec-G expression and impaired cytotoxicity, and granzyme B expression significantly increased with sialidase treatment of stromal cells. In an inflammatory tumor model, inflammatory tumor-conditioned MSCs (MSC\n                      <jats:sup>iTCS<\/jats:sup>\n                      ) promoted metastasis and Siglec-G induction on NK cells and macrophages, both reversed by sialyltransferase inhibition, underscoring the effects of stromal modulation of innate immune cell function in inflammatory tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Stromal cell sialylation modulates innate immune suppression in CRC via the sialic acid\/Siglec axis. Targeting stromal sialylation restores NK cytotoxicity and macrophage activation, offering novel insights that may shape therapeutic strategies for reversing immunosuppression in stromal-rich tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012491","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T02:45:10Z","timestamp":1760928310000},"page":"e012491","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Stromal cells modulate innate immune cell phenotype and function in colorectal cancer via the Sialic acid\/Siglec axis"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2390-1351","authenticated-orcid":false,"given":"Aoise","family":"O\u2019Neill","sequence":"first","affiliation":[{"name":"Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2589-1543","authenticated-orcid":false,"given":"Norashikin","family":"Zakaria","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Bull","sequence":"additional","affiliation":[{"name":"Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Egan","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shania M","family":"Corry","sequence":"additional","affiliation":[{"name":"Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK"},{"name":"Centre for Human Genetics, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh A","family":"Leonard","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4123-2799","authenticated-orcid":false,"given":"Clodagh","family":"O\u2019Meara","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4760-7996","authenticated-orcid":false,"given":"Linda","family":"Howard","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasija","family":"Walsh","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Reidy","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"C\u00daRAM Centre for Research in Medical Devices, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3181-0848","authenticated-orcid":false,"given":"Jenny","family":"Che","sequence":"additional","affiliation":[{"name":"Palleon Pharmaceuticals, Waltham, MA 02451, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Peng","sequence":"additional","affiliation":[{"name":"Palleon Pharmaceuticals, Waltham, MA 02451, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3725-0057","authenticated-orcid":false,"given":"Lizhi","family":"Cao","sequence":"additional","affiliation":[{"name":"Palleon Pharmaceuticals, Waltham, MA 02451, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence J","family":"Egan","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7709-8489","authenticated-orcid":false,"given":"Thomas","family":"Ritter","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"C\u00daRAM Centre for Research in Medical Devices, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Sheehan","sequence":"additional","affiliation":[{"name":"Division of Anatomical Pathology, Galway University Hospital, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoife","family":"Canney","sequence":"additional","affiliation":[{"name":"Division of Anatomical Pathology, Galway University Hospital, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Culligan","sequence":"additional","affiliation":[{"name":"Division of Anatomical Pathology, Galway University Hospital, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisling M","family":"Hogan","sequence":"additional","affiliation":[{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Department of Colorectal Surgery, Galway University Hospital, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean O","family":"Hynes","sequence":"additional","affiliation":[{"name":"Division of Anatomical Pathology, Galway University Hospital, Galway, Ireland"},{"name":"Discipline of Pathology, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip D","family":"Dunne","sequence":"additional","affiliation":[{"name":"Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK"},{"name":"Cancer Research UK Scotland Institute, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"O\u2019Dwyer","sequence":"additional","affiliation":[{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Discipline of Medicine, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3898-9806","authenticated-orcid":false,"given":"Oliver","family":"Treacy","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-6783","authenticated-orcid":false,"given":"Aideen E","family":"Ryan","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"},{"name":"C\u00daRAM Centre for Research in Medical Devices, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,10,19]]},"reference":[{"key":"2025111301350671000_13.10.e012491.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"2025111301350671000_13.10.e012491.2","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1403533","article-title":"Immune checkpoint inhibitors in colorectal cancer: limitation and challenges","volume":"15","author":"Yan","year":"2024","journal-title":"Front Immunol"},{"key":"2025111301350671000_13.10.e012491.3","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3967"},{"key":"2025111301350671000_13.10.e012491.4","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djab106"},{"key":"2025111301350671000_13.10.e012491.5","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.969855","article-title":"Consensus molecular subtype 4 (CMS4)-targeted therapy in primary colon cancer: A proof-of-concept study","volume":"12","author":"Peters","year":"2022","journal-title":"Front Oncol"},{"key":"2025111301350671000_13.10.e012491.6","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-23-3964"},{"key":"2025111301350671000_13.10.e012491.7","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-41518-w","article-title":"The tumor microenvironment shows a hierarchy of cell-cell interactions dominated by fibroblasts","volume":"14","author":"Mayer","year":"2023","journal-title":"Nat Commun"},{"key":"2025111301350671000_13.10.e012491.8","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-4141"},{"key":"2025111301350671000_13.10.e012491.9","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-013-0663-z"},{"key":"2025111301350671000_13.10.e012491.10","doi-asserted-by":"crossref","first-page":"4037","DOI":"10.1111\/cas.15081","article-title":"Improving function of cytotoxic T-lymphocytes by transforming growth factor-\u03b2 inhibitor in oral squamous cell carcinoma","volume":"112","author":"Kondo","year":"2021","journal-title":"Cancer Sci"},{"key":"2025111301350671000_13.10.e012491.11","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14374"},{"key":"2025111301350671000_13.10.e012491.12","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-06654-8","article-title":"TGF-\u03b2-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure","volume":"9","author":"Chakravarthy","year":"2018","journal-title":"Nat Commun"},{"key":"2025111301350671000_13.10.e012491.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.01.011"},{"key":"2025111301350671000_13.10.e012491.14","doi-asserted-by":"crossref","first-page":"620688","DOI":"10.3389\/fonc.2021.620688","article-title":"Immunosuppressive Microenvironment Revealed by Immune Cell Landscape in Pre-metastatic Liver of Colorectal Cancer","volume":"11","author":"Zeng","year":"2021","journal-title":"Front Oncol"},{"key":"2025111301350671000_13.10.e012491.15","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1155085","article-title":"The tumor stroma influences immune cell distribution and recruitment in a PDAC-on-a-chip model","volume":"14","author":"Geyer","year":"2023","journal-title":"Front Immunol"},{"key":"2025111301350671000_13.10.e012491.16","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1158\/1541-7786.MCR-21-0960","article-title":"Stromal p53 Regulates Breast Cancer Development, the Immune Landscape, and Survival in an Oncogene-Specific Manner","volume":"20","author":"Wu","year":"2022","journal-title":"Mol Cancer Res"},{"key":"2025111301350671000_13.10.e012491.17","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2024.110701","article-title":"Tumor-associated mesenchymal stromal cells modulate macrophage phagocytosis in stromal-rich colorectal cancer via PD-1 signaling","volume":"27","author":"Leonard","year":"2024","journal-title":"iScience"},{"key":"2025111301350671000_13.10.e012491.18","doi-asserted-by":"publisher","DOI":"10.1038\/nri3902"},{"key":"2025111301350671000_13.10.e012491.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.09.011"},{"key":"2025111301350671000_13.10.e012491.20","doi-asserted-by":"crossref","first-page":"112475","DOI":"10.1016\/j.celrep.2023.112475","article-title":"Targeting stromal cell sialylation reverses T cell-mediated immunosuppression in the tumor microenvironment","volume":"42","author":"Egan","year":"2023","journal-title":"Cell Rep"},{"key":"2025111301350671000_13.10.e012491.21","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0426"},{"key":"2025111301350671000_13.10.e012491.22","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s42003-023-05733-x","article-title":"Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer","volume":"7","author":"Zhang","year":"2024","journal-title":"Commun Biol"},{"key":"2025111301350671000_13.10.e012491.23","doi-asserted-by":"crossref","first-page":"216985","DOI":"10.1016\/j.canlet.2024.216985","article-title":"Colorectal cancer-associated fibroblasts inhibit effector T cells via NECTIN2 signaling","volume":"595","author":"Agorku","year":"2024","journal-title":"Cancer Lett"},{"key":"2025111301350671000_13.10.e012491.24","doi-asserted-by":"crossref","DOI":"10.1038\/s42003-024-06087-8","article-title":"Pancreatic cancer-associated fibroblasts modulate macrophage differentiation via sialic acid-Siglec interactions","volume":"7","author":"Boelaars","year":"2024","journal-title":"Commun Biol"},{"key":"2025111301350671000_13.10.e012491.25","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-21550-4","article-title":"Sialic acids in pancreatic cancer cells drive tumour-associated macrophage differentiation via the Siglec receptors Siglec-7 and Siglec-9","volume":"12","author":"Rodriguez","year":"2021","journal-title":"Nat Commun"},{"key":"2025111301350671000_13.10.e012491.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.02.001"},{"key":"2025111301350671000_13.10.e012491.27","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41420-024-02180-3","article-title":"Biological function of sialic acid and sialylation in human health and disease","volume":"10","author":"Zhu","year":"2024","journal-title":"Cell Death Discov"},{"key":"2025111301350671000_13.10.e012491.28","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2019.1667977"},{"key":"2025111301350671000_13.10.e012491.29","doi-asserted-by":"publisher","DOI":"10.1038\/nri2056"},{"key":"2025111301350671000_13.10.e012491.30","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075018"},{"key":"2025111301350671000_13.10.e012491.31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00262-023-03606-0","article-title":"Targeting CD24\/Siglec-10 signal pathway for cancer immunotherapy: recent advances and future directions","volume":"73","author":"Li","year":"2024","journal-title":"Cancer Immunol Immunother"},{"key":"2025111301350671000_13.10.e012491.32","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41586-019-1456-0","article-title":"CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy","volume":"572","author":"Barkal","year":"2019","journal-title":"Nature New Biol"},{"key":"2025111301350671000_13.10.e012491.33","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202403438","article-title":"Siglec\u2010G Suppresses CD8 + T Cells Responses through Metabolic Rewiring and Can be Targeted to Enhance Tumor Immunotherapy","volume":"11","author":"Yin","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"2025111301350671000_13.10.e012491.34","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.jhep.2024.01.028","article-title":"Increased Siglec-9\/Siglec-9L interactions on NK cells predict poor HCC prognosis and present a targetable checkpoint for immunotherapy","volume":"80","author":"Xiao","year":"2024","journal-title":"J Hepatol"},{"key":"2025111301350671000_13.10.e012491.35","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1093\/abt\/tbad020","article-title":"IMM47, a humanized monoclonal antibody that targets CD24, exhibits exceptional anti-tumor efficacy by blocking the CD24\/Siglec-10 interaction and can be used as monotherapy or in combination with anti-PD1 antibodies for cancer immunotherapy","volume":"6","author":"Li","year":"2023","journal-title":"Antibody Therapeutics"},{"key":"2025111301350671000_13.10.e012491.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2022.101112"},{"key":"2025111301350671000_13.10.e012491.37","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-52212-2","article-title":"PSGL-1 decorated with sialyl Lewisa\/x promotes high affinity binding of myeloma cells to P-selectin but is dispensable for E-selectin engagement","volume":"14","author":"O\u2019Dwyer","year":"2024","journal-title":"Sci Rep"},{"key":"2025111301350671000_13.10.e012491.38","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021006805"},{"key":"2025111301350671000_13.10.e012491.39","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acr.2022.07.003"},{"key":"2025111301350671000_13.10.e012491.40","doi-asserted-by":"crossref","DOI":"10.3390\/cells10051260","article-title":"Siglec Ligands","volume":"10","author":"Gonzalez-Gil","year":"2021","journal-title":"Cells"},{"key":"2025111301350671000_13.10.e012491.41","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.trecan.2016.07.008","article-title":"Colorectal Cancer Subtypes: Developmental Origin and Microenvironmental Regulation","volume":"2","author":"Fessler","year":"2016","journal-title":"Trends Cancer"},{"key":"2025111301350671000_13.10.e012491.42","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-326183"},{"key":"2025111301350671000_13.10.e012491.43","article-title":"Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors","volume":"5","author":"Gy\u0151rffy","year":"2024","journal-title":"Innovation (Camb)"},{"key":"2025111301350671000_13.10.e012491.44","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.trecan.2023.11.009","article-title":"Targeting myeloid cells for cancer immunotherapy: Siglec-7\/9\/10\/15 and their ligands","volume":"10","author":"Boelaars","year":"2024","journal-title":"Trends Cancer"},{"key":"2025111301350671000_13.10.e012491.45","doi-asserted-by":"crossref","first-page":"6206","DOI":"10.1111\/febs.15647","article-title":"Tools to study and target the Siglec-sialic acid axis in cancer","volume":"288","author":"L\u00e4ubli","year":"2021","journal-title":"FEBS J"},{"key":"2025111301350671000_13.10.e012491.46","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-63103-x","article-title":"Changes in subset distribution and impaired function of circulating natural killer cells in patients with colorectal cancer","volume":"14","author":"Zu","year":"2024","journal-title":"Sci Rep"},{"key":"2025111301350671000_13.10.e012491.47","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-019-1435-2","article-title":"Cancer-associated fibroblasts enhance tumor-associated macrophages enrichment and suppress NK cells function in colorectal cancer","volume":"10","author":"Zhang","year":"2019","journal-title":"Cell Death Dis"},{"key":"2025111301350671000_13.10.e012491.48","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65899"},{"key":"2025111301350671000_13.10.e012491.49","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/s13402-024-00926-w","article-title":"The prognostic effect of tumor-associated macrophages in stage I-III colorectal cancer depends on T cell infiltration","volume":"47","author":"Majid","year":"2024","journal-title":"Cell Oncol"},{"key":"2025111301350671000_13.10.e012491.50","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0443"},{"key":"2025111301350671000_13.10.e012491.51","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-05694-x","article-title":"Dynamic increase of M2 macrophages is associated with disease progression of colorectal cancers following cetuximab-based treatment","volume":"12","author":"Kim","year":"2022","journal-title":"Sci Rep"},{"key":"2025111301350671000_13.10.e012491.52","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202102620","article-title":"Colorectal Cancer-Derived Small Extracellular Vesicles Promote Tumor Immune Evasion by Upregulating PD-L1 Expression in Tumor-Associated Macrophages","volume":"9","author":"Yin","year":"2022","journal-title":"Adv Sci (Weinh)"},{"key":"2025111301350671000_13.10.e012491.53","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1007\/s11605-017-3446-6","article-title":"Increased Infiltration of Natural Killer and T Cells in Colorectal Liver Metastases Improves Patient Overall Survival","volume":"21","author":"Donadon","year":"2017","journal-title":"J Gastrointest Surg"},{"key":"2025111301350671000_13.10.e012491.54","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-21-0772"},{"key":"2025111301350671000_13.10.e012491.55","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25116188","article-title":"The Crucial Role of Inflammation and the Immune System in Colorectal Cancer Carcinogenesis: A Comprehensive Perspective","volume":"25","author":"Burgos-Molina","year":"2024","journal-title":"Int J Mol Sci"},{"key":"2025111301350671000_13.10.e012491.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2014.07.005"},{"key":"2025111301350671000_13.10.e012491.57","doi-asserted-by":"publisher","DOI":"10.5009\/gnl.2013.7.6.629"},{"key":"2025111301350671000_13.10.e012491.58","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3614"},{"key":"2025111301350671000_13.10.e012491.59","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20061118"},{"key":"2025111301350671000_13.10.e012491.60","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.799861","article-title":"The Distinct Roles of Sialyltransferases in Cancer Biology and Onco-Immunology","volume":"12","author":"Hugonnet","year":"2021","journal-title":"Front Immunol"},{"key":"2025111301350671000_13.10.e012491.61","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.236.1"},{"key":"2025111301350671000_13.10.e012491.62","doi-asserted-by":"publisher","DOI":"10.1002\/PATH.6152"},{"key":"2025111301350671000_13.10.e012491.63","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abj1270","article-title":"Targeting cancer glycosylation repolarizes tumor-associated macrophages allowing effective immune checkpoint blockade","volume":"14","author":"Stanczak","year":"2022","journal-title":"Sci Transl Med"},{"key":"2025111301350671000_13.10.e012491.64","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.233"},{"key":"2025111301350671000_13.10.e012491.65","doi-asserted-by":"crossref","DOI":"10.1002\/eji.70000","article-title":"The Tumour Glyco-Code: Sialylation as a Mediator of Stromal Cell Immunosuppression in the Tumour Microenvironment","volume":"55","author":"O\u2019Neill","year":"2025","journal-title":"Eur J Immunol"},{"key":"2025111301350671000_13.10.e012491.66","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001453","article-title":"Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value","volume":"10","author":"Marisa","year":"2013","journal-title":"PLoS Med"},{"key":"2025111301350671000_13.10.e012491.67","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2025111301350671000_13.10.e012491.68","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr260"},{"key":"2025111301350671000_13.10.e012491.69","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"2025111301350671000_13.10.e012491.70","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313"},{"key":"2025111301350671000_13.10.e012491.71","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu393"},{"key":"2025111301350671000_13.10.e012491.72","doi-asserted-by":"crossref","unstructured":"Wickham H . ggplot2: elegant graphics for data analysis. New York: Springer-Verlag, 2016.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"2025111301350671000_13.10.e012491.73","unstructured":"Clarke E . ggbeeswarm: categorical scatter (violin point) plots, version 0.7.2. 2023."},{"key":"2025111301350671000_13.10.e012491.74","unstructured":"Kassambara A . ggpubr: \u201cggplot2\u201d based publication ready plots. CRAN; 2023."},{"key":"2025111301350671000_13.10.e012491.75","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16747-x"},{"key":"2025111301350671000_13.10.e012491.76","unstructured":"Team, R.C . R: a language and environment for statistical computing. R foundation for statistical computing, Vienna, Austria. 2022. Available: https:\/\/www.R-project.org\/"},{"key":"2025111301350671000_13.10.e012491.77","doi-asserted-by":"crossref","unstructured":"Wickham, ggplot2: elegant graphics for data analysis: springer-verlag New York. 2016.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"2025111301350671000_13.10.e012491.78","unstructured":"Kassambara A , Kosinski M . B. P. survminer: drawing survival curves using \u201cggplot2\u201d, R package version 0.5.0. 2024. Available: https:\/\/rpkgs.datanovia.com\/survminer\/index.html"},{"key":"2025111301350671000_13.10.e012491.79","unstructured":"Wiesweg M . survivalAnalysis: high-level interface for survival analysis and associated Plots_.R package version 0.4.0, 2025. Available: https:\/\/CRAN.R-project.org\/package=survivalAnalysis"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-012491","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:35:21Z","timestamp":1763026521000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-012491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":79,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,19]]},"published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1136\/jitc-2025-012491"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-012491","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]}}}