{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T22:32:19Z","timestamp":1780612339143,"version":"3.54.1"},"reference-count":48,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jagiellonian University","award":["K\/ZDS\/006392"],"award-info":[{"award-number":["K\/ZDS\/006392"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response against cancer in SLNs. METHODS: In SLNs excisions obtained from 123 invasive BC patients, we performed immunohistochemistry (IHC) for CD1a, CD1c, DC-LAMP, and DC-SIGN to identify different DCs populations. Then we investigated the numbers of DCs subsets in tumor-free, micrometastatic, and macrometastatic SLNs with the use of a light microscope. RESULTS: We observed that CD1c+ and DC-SIGN+ DCs were more numerous in SLNs with a larger tumor size. More abundant intratumoral DC-LAMP+ population was related to a higher number of metastatic lymph nodes. Conversely, more abundant CD1a+ DCs were associated with a decreasing nodal burden in SLNs and a lower number of involved lymph nodes. Moreover, densities of the investigated DC populations differed with respect to tumor grade, HER2 overexpression, hormone receptor status, and histologic type of BC. CONCLUSIONS: According to their subtype, DCs are associated with either lower or higher nodal burden in SLNs from invasive BC patients. These relationships appear to be dependent not only on the maturation state of DCs but also on the histological and biological characteristics of the tumor.<\/jats:p>","DOI":"10.3390\/ijms23158461","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T02:06:42Z","timestamp":1659319602000},"page":"8461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1267-6257","authenticated-orcid":false,"given":"Joanna","family":"Szpor","sequence":"first","affiliation":[{"name":"Department of Pathomorphology, Jagiellonian University Medical College, 31-008 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Streb","sequence":"additional","affiliation":[{"name":"Department of Oncology, Jagiellonian University Medical College, 31-008 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Glajcar","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Jagiellonian University Medical College, 31-008 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2923-5212","authenticated-orcid":false,"given":"Piotr","family":"Sadowski","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Jagiellonian University Medical College, 31-008 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Streb-Smole\u0144","sequence":"additional","affiliation":[{"name":"Department of Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 00-001 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5512-763X","authenticated-orcid":false,"given":"Robert","family":"Jach","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Oncology, Jagiellonian University Medical College, 31-008 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Hodorowicz-Zaniewska","sequence":"additional","affiliation":[{"name":"General, Oncological and Gastrointestinal Surgery, Jagiellonian University Medical College, 31-008 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ejso.2017.10.215","article-title":"Controversies and recommendations regarding sentinel lymph node biopsy in primary breast cancer: A comprehensive review of current data","volume":"44","author":"Charalampoudis","year":"2018","journal-title":"Eur. J. Surg. Oncol. (EJSO)"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/nri1919","article-title":"Tumour\u2013induced immune modulation of sentinel lymph nodes","volume":"6","author":"Cochran","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.surge.2016.07.002","article-title":"Micro- and macro-metastasis in the axillary lymph node: A review","volume":"15","author":"Naidoo","year":"2017","journal-title":"Surgeon"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.critrevonc.2018.06.013","article-title":"Critical review of axillary recurrence in early breast cancer","volume":"129","author":"Castaneda","year":"2018","journal-title":"Crit. Rev. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R408","DOI":"10.1186\/bcr808","article-title":"Analysis of dendritic cells in tumor-free and tumor-containing sentinel lymph nodes from patients with breast cancer","volume":"6","author":"Poindexter","year":"2004","journal-title":"Breast Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/IGC.0b013e3181b3e616","article-title":"Analysis of Dendritic Cells in Sentinel Lymph Nodes of Patients with Endometrial and Patients with Cervical Cancers","volume":"19","author":"Kara","year":"2009","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hossain, K., and Wall, K.A. (2019). Use of Dendritic Cell Receptors as Targets for Enhancing Anti-Cancer Immune Responses. Cancers, 11.","DOI":"10.3390\/cancers11030418"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3892\/etm.2014.2059","article-title":"Inhibition of vascular endothelial growth factor by small interfering RNA upregulates differentiation, maturation and function of dendritic cells","volume":"9","author":"Wang","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.cellimm.2017.08.007","article-title":"High Antigen Processing Machinery component expression in Langerhans cells from melanoma patients\u2019 sentinel lymph nodes","volume":"320","author":"Romoli","year":"2017","journal-title":"Cell. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/j.1365-3083.2011.02652.x","article-title":"Activated Monocytes Prime Na\u00efve T Cells Against Autologous Cancer: Vigorous Cancer Destruction In Vitro and In Vivo","volume":"75","author":"Laumbacher","year":"2012","journal-title":"Scand. J. Immunol."},{"key":"ref_11","first-page":"237","article-title":"CD1c+ and CD303+ dendritic cells in peripheral blood, lymph nodes and tumor tissue of patients with non-small cell lung cancer","volume":"19","author":"Tabarkiewicz","year":"2008","journal-title":"Oncol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41523-018-0081-7","article-title":"Sentinel lymph node B cells can predict disease-free survival in breast cancer patients","volume":"4","author":"Blenman","year":"2018","journal-title":"NPJ Breast Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.0300-9475.2005.01531.x","article-title":"Phenotypic and Functional Characterization of Clinical Grade Dendritic Cells Generated from Patients with Advanced Breast Cancer for Therapeutic Vaccination","volume":"61","author":"Pedersen","year":"2005","journal-title":"Scand. J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/cncr.21729","article-title":"Maturation of dendritic cells and T-cell responses in sentinel lymph nodes from patients with breast carcinoma","volume":"106","author":"Matsuura","year":"2006","journal-title":"Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"808","DOI":"10.4049\/jimmunol.181.1.808","article-title":"Fusions of Dendritic Cells with Breast Carcinoma Stimulate the Expansion of Regulatory T Cells while Concomitant Exposure to IL-12, CpG Oligodeoxynucleotides, and Anti-CD3\/CD28 Promotes the Expansion of Activated Tumor Reactive  Cells","volume":"181","author":"Vasir","year":"2008","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Szpor, J., Streb, J., Glajcar, A., Fr\u0105czek, P., Winiarska, A., Tyrak, K., Basta, P., Oko\u0144, K., Jach, R., and Hodorowicz-Zaniewska, D. (2021). Dendritic Cells Are Associated with Prognosis and Survival in Breast Cancer. Diagnostics, 11.","DOI":"10.3390\/diagnostics11040702"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/jop.12039","article-title":"Immune response in cervical lymph nodes from patients with primary oral squamous cell carcinoma","volume":"42","author":"Costa","year":"2013","journal-title":"J. Oral Pathol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1182\/blood-2011-03-344838","article-title":"Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation","volume":"118","author":"Hout","year":"2011","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/icb.2011.25","article-title":"Preferential Langerhans cell differentiation from CD34+precursors upon introduction of ABCG2 (BCRP)","volume":"90","author":"Ven","year":"2012","journal-title":"Immunol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/path.1344","article-title":"Recruitment of immature plasmacytoid dendritic cells (plasmacytoid monocytes) and myeloid dendritic cells in primary cutaneous melanomas","volume":"200","author":"Vermi","year":"2003","journal-title":"J. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1002\/ijc.20146","article-title":"Breast carcinoma cells promote the differentiation of CD34+ progenitors towards 2 different subpopulations of dendritic cells with CD1ahighCD86?Langerin- and CD1a+CD86+Langerin+ phenotypes","volume":"110","author":"Thomachot","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1365-2559.2007.02919.x","article-title":"CD1a down-regulation in primary invasive ductal breast carcinoma may predict regional lymph node invasion and patient outcome","volume":"52","author":"Anzalone","year":"2008","journal-title":"Histopathology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1007\/s12282-021-01270-9","article-title":"CD1a- and CD83-positive dendritic cells as prognostic markers of metastasis development in early breast cancer patients","volume":"28","author":"Giorello","year":"2021","journal-title":"Breast Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kohrt, H., Nouri, N., Nowels, K., Johnson, D., Holmes, S., and Lee, P.P. (2005). Profile of Immune Cells in Axillary Lymph Nodes Predicts Disease-Free Survival in Breast Cancer. PLoS Med., 2.","DOI":"10.1371\/journal.pmed.0020284"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00428-011-1145-3","article-title":"Metastasis to sentinel lymph nodes in breast cancer is associated with maturation arrest of dendritic cells and poor co-localization of dendritic cells and CD8+ T cells","volume":"459","author":"Mansfield","year":"2011","journal-title":"Virchows Arch."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.molimm.2012.10.019","article-title":"Diverse antigen presentation by the Group 1 CD1 molecule, CD1c","volume":"55","author":"Adams","year":"2013","journal-title":"Mol. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.immuni.2020.06.002","article-title":"Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells","volume":"53","author":"Bourdely","year":"2020","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1038\/s41467-018-04985-0","article-title":"Human in vivo-generated monocyte-derived dendritic cells and macrophages cross-present antigens through a vacuolar pathway","volume":"9","author":"Gueguen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1002\/eji.201142098","article-title":"Human CD1c (BDCA-1)+ myeloid dendritic cells secrete IL-10 and display an immuno-regulatory phenotype and function in response to Escherichia coli","volume":"42","author":"Kassianos","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.cell.2017.04.014","article-title":"Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses","volume":"169","author":"Lavin","year":"2017","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.3748\/wjg.v24.i11.1228","article-title":"Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and premalignant hepatic lesions","volume":"24","author":"Zekri","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6803756","DOI":"10.1155\/2017\/6803756","article-title":"Melanomas and Dysplastic Nevi Differ in Epidermal CD1c+ Dendritic Cell Count","volume":"2017","author":"Dyduch","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.canlet.2007.04.003","article-title":"Distribution of dendritic cell subtypes in primary oral squamous cell carcinoma is inconsistent with a functional response","volume":"255","author":"Mick","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1158\/0008-5472.CAN-03-2969","article-title":"Selective Accumulation of Mature DC-Lamp+ Dendritic Cells in Tumor Sites Is Associated with Efficient T-Cell-Mediated Antitumor Response and Control of Metastatic Dissemination in Melanoma","volume":"64","author":"Movassagh","year":"2004","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3825","DOI":"10.1158\/1078-0432.CCR-07-0358","article-title":"Long-Term Protective Effect of Mature DC-LAMP+ Dendritic Cell Accumulation in Sentinel Lymph Nodes Containing Micrometastatic Melanoma","volume":"13","author":"Elliott","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_36","first-page":"279","article-title":"DC-SIGN and immunoregulation","volume":"3","author":"Zhou","year":"2006","journal-title":"Cell. Mol. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.tracli.2017.08.002","article-title":"Differentiation of human dendritic cell subsets for immune tolerance induction","volume":"25","author":"Lamendour","year":"2018","journal-title":"Transfus. Clin. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.4049\/jimmunol.1000475","article-title":"Dendritic Cell-Specific ICAM-3\u2013Grabbing Nonintegrin Expression on M2-Polarized and Tumor-Associated Macrophages Is Macrophage-CSF Dependent and Enhanced by Tumor-Derived IL-6 and IL-10","volume":"186","author":"Corcuera","year":"2011","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e1629257","DOI":"10.1080\/2162402X.2019.1629257","article-title":"Aberrant fucosylation enables breast cancer clusterin to interact with dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN)","volume":"8","author":"Merlotti","year":"2019","journal-title":"OncoImmunology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e955331","DOI":"10.4161\/21624011.2014.955331","article-title":"Tumor stroma-derived factors skew monocyte to dendritic cell differentiation toward a suppressive CD14+PD-L1+phenotype in prostate cancer","volume":"3","author":"Spary","year":"2014","journal-title":"OncoImmunology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.2353\/ajpath.2010.090908","article-title":"Expression of Vascular Notch Ligand Delta-Like 4 and Inflammatory Markers in Breast Cancer","volume":"176","author":"Jubb","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1155\/2011\/291769","article-title":"Lymphatic expression of CLEVER-1 in breast cancer and its relationship with lymph node metastasis","volume":"34","author":"Ammar","year":"2011","journal-title":"Anal. Cell. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.4049\/jimmunol.0804140","article-title":"Early Recycling Compartment Trafficking of CD1a Is Essential for Its Intersection and Presentation of Lipid Antigens","volume":"184","author":"Cernadas","year":"2010","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.ejso.2007.05.013","article-title":"Presence of mature DC-Lamp+ dendritic cells in sentinel and non-sentinel lymph nodes of breast cancer patients","volume":"34","author":"Bembenek","year":"2008","journal-title":"Eur. J. Surg. Oncol. (EJSO)"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3322\/caac.21393","article-title":"Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual","volume":"67","author":"Giuliano","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_46","unstructured":"Hiram, S.C. (2002). The isotope technique. Sentinel Lymph Node Biopsy, Martin Dunitz Ltd."},{"key":"ref_47","unstructured":"Schauer, A., Becker, W., and Reiser, M.F. (2004). Sentinel Lymph Node Concept, Springer."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1200\/JCO.2013.50.9984","article-title":"Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology\/College of American Pathologists Clinical Practice Guideline Update","volume":"31","author":"Wolff","year":"2013","journal-title":"J. Clin. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8461\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:59:57Z","timestamp":1760140797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,30]]},"references-count":48,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23158461"],"URL":"https:\/\/doi.org\/10.3390\/ijms23158461","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,30]]}}}