{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T11:54:08Z","timestamp":1792929248837,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K16913"],"award-info":[{"award-number":["22K16913"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JS20220057"],"award-info":[{"award-number":["JS20220057"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Soda Toyoji Memorial Foundation","award":["22K16913"],"award-info":[{"award-number":["22K16913"]}]},{"name":"Soda Toyoji Memorial Foundation","award":["JS20220057"],"award-info":[{"award-number":["JS20220057"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dendritic cells (DCs) are known to be major antigen-presenting cells, and lymph nodes (LNs) play an important role in DC-mediated immune response. CD1a is known as a marker of monocyte-derived DCs. The present study focused on the infiltration of CD1a-positive DCs (CD1a-DCs) into regional LNs in 70 cases of gallbladder cancer (GBC). After univariate analyses, the results showed that LN infiltration by CD1a-DCs was associated with unfavorable clinical outcomes in patients with GBC, with all cases categorized in the CD1a-DCs high group had nodal metastasis. LN infiltration by CD1a-DCs was not an independent prognostic factor identified by multivariate analyses. After subgroup analyses of cases with LN metastasis (n = 32), no significant impacts of CD1a-DCs infiltration into metastatic LNs were observed. In contrast, CD1a-DCs infiltration into primary tumors had a significant impact on surgical outcomes. The results of strong confounding between CD1a-DCs and LN metastasis support the theory that CD1a-DCs are developed from monocytes at tumor sites. As the results of previous research focused on CD1a-DCs infiltration into regional LNs of other organs varied, the role and significance of CD1a-DCs infiltration in regional LNs may be different according to the tumor histology or its primary site. Thus, further studies are needed to clarify the role and significance of CD1a-DCs infiltration into regional LNs of solid cancers.<\/jats:p>","DOI":"10.3390\/ijms252312763","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T10:05:56Z","timestamp":1732701956000},"page":"12763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analysis of CD1a-Positive Monocyte-Derived Cells in the Regional Lymph Nodes of Patients with Gallbladder Cancer"],"prefix":"10.3390","volume":"25","author":[{"given":"Sachiko","family":"Maeda","sequence":"first","affiliation":[{"name":"Department of Pathology & Microbiology, Faculty of Medicine, Saga University, Saga 849-8501, Japan"},{"name":"Department of Surgery, Faculty of Medicine, Saga University, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-2598","authenticated-orcid":false,"given":"Keita","family":"Kai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saga University Hospital, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Department of Pathology & Microbiology, Faculty of Medicine, Saga University, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomokazu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine, Saga University, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Ide","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine, Saga University, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Noshiro","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine, Saga University, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/jhbp.314","article-title":"Biliary tract cancer registry in Japan from 2008 to 2013","volume":"23","author":"Ishihara","year":"2016","journal-title":"J. Hepato-Biliary-Pancreatic Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1097\/SLA.0b013e3181b5d5fc","article-title":"Differential diagnostic and staging accuracies of high resolution ultrasonography, endoscopic ultrasonography, and multidetector computed tomography for gallbladder polypoid lesions and gallbladder cancer","volume":"250","author":"Jang","year":"2009","journal-title":"Ann. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00281-016-0583-z","article-title":"Dendritic cells as gatekeepers of tolerance","volume":"39","author":"Waisman","year":"2017","journal-title":"Semin. Immunopathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1126\/science.1178331","article-title":"Development of monocytes, macrophages, and dendritic cells","volume":"5966","author":"Geissmann","year":"2010","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Patente, T.A., Pinho, M.P., Oliveira, A.A., Evangelista, G.C.M., Bergami-Santos, P.C., and Barbuto, J.A.M. (2019). Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.03176"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.critrevonc.2016.09.002","article-title":"Migration of dendritic cells to the lymph nodes and its enhancement to drive anti-tumor responses","volume":"107","author":"Seyfizadeh","year":"2016","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"310","DOI":"10.14348\/molcells.2021.0059","article-title":"Current Understanding of the Roles of CD1a-Restricted T Cells in the Immune System","volume":"44","author":"Yoo","year":"2021","journal-title":"Mol. Cells."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.imbio.2014.12.010","article-title":"Myeloid dendritic cells: Development, functions, and role in atherosclerotic inflammation","volume":"220","author":"Chistiakov","year":"2015","journal-title":"Immunobiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/nri3712","article-title":"Dendritic cells, monocytes and macrophages: A unified nomenclature based on ontogeny","volume":"14","author":"Guilliams","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1084\/jem.20120340","article-title":"Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages","volume":"209","author":"Hoeffel","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.it.2023.10.005","article-title":"Monocyte differentiation within tissues: A renewed outlook","volume":"44","author":"Rigamonti","year":"2023","journal-title":"Trends Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1146\/annurev-immunol-061020-053707","article-title":"Dendritic Cells Revisited","volume":"39","author":"Cardoso","year":"2021","journal-title":"Annu. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.4049\/jimmunol.1600777","article-title":"Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets","volume":"198","author":"Patel","year":"2017","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1038\/s41467-021-22375-x","article-title":"Human anogenital monocyte-derived dendritic cells and langerin+cDC2 are major HIV target cells","volume":"12","author":"Rhodes","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"100923","DOI":"10.1016\/j.tranon.2020.100923","article-title":"Immunohistochemical analysis of the aggregation of CD1a-positive dendritic cells in resected specimens and its association with surgical outcomes for patients with gallbladder cancer","volume":"14","author":"Kai","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_17","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_18","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_19","doi-asserted-by":"crossref","unstructured":"Kawasaki, K., Kai, K., Minesaki, A., Maeda, S., Yamauchi, M., and Kuratomi, Y. (2024). Chemoradiotherapy and Lymph Node Metastasis Affect Dendritic Cell Infiltration and Maturation in Regional Lymph Nodes of Laryngeal Cancer. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202401.1492.v1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0952-7915(00)00180-1","article-title":"The cell biology of antigen presentation in dendritic cells","volume":"13","author":"Amigorena","year":"2001","journal-title":"Curr. Opin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.immuni.2004.06.014","article-title":"CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions","volume":"21","author":"Ohl","year":"2004","journal-title":"Immunity"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Brandum, E.P., J\u00f8rgensen, A.S., Rosenkilde, M.M., and Hjort\u00f8, G.M. (2021). Dendritic Cells and CCR7 Expression: An Important Factor for Autoimmune Diseases, Chronic Inflammation, and Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158340"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1126\/science.1228456","article-title":"Interstitial dendritic cell guidance by haptotactic chemokine gradients","volume":"339","author":"Weber","year":"2013","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.it.2016.09.006","article-title":"Dendritic Cells and Cancer Immunity","volume":"37","author":"Gardner","year":"2016","journal-title":"Trends Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/j.1524-4741.2009.00707.x","article-title":"Dendritic cell infiltration in lymph node positive breast carcinomas","volume":"15","author":"He","year":"2009","journal-title":"Breast J."},{"key":"ref_26","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_27","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_28","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_29","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s13139-009-0002-7","article-title":"Tc-99m diphosphonate as a potential radiotracer to detect sentinel lymph nodes in patients with breast cancer","volume":"44","author":"Yang","year":"2010","journal-title":"Nucl. Med. Mol. Imaging"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1159\/000513502","article-title":"Higher CD1a Levels Correlate with PD-L1 Expression and Predict Worse Overall Survival in Triple-Negative Breast Carcinoma","volume":"17","author":"Zheng","year":"2022","journal-title":"Breast Care"},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/00008390-200504000-00003","article-title":"Cytokine expression and dendritic cell density in melanoma sentinel nodes","volume":"15","author":"Ramos","year":"2005","journal-title":"Melanoma Res."},{"key":"ref_33","first-page":"969","article-title":"Melanoma Sequentially Suppresses Different DC Subsets in the Sentinel Lymph Node, Affecting Disease Spread and Recurrence","volume":"11","author":"Koster","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/00008390-200306000-00007","article-title":"Dendritic cell density and activation status of tumour-infiltrating lymphocytes in metastatic human melanoma: Possible implications for sentinel node metastases","volume":"13","author":"Barbour","year":"2003","journal-title":"Melanoma Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.oraloncology.2004.07.004","article-title":"Infiltration of dendritic cells and NK cells into the sentinel lymph node in oral cavity cancer","volume":"41","author":"Sakakura","year":"2005","journal-title":"Oral. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.3892\/or_00001003","article-title":"Evaluation of immune response according to the metastatic status in the regional lymph nodes in patients with gastric carcinoma","volume":"24","author":"Nakamura","year":"2010","journal-title":"Oncol. Rep."},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0003-9969(94)00152-2","article-title":"Induction of the CD1a Langerhans cell marker on human monocytes","volume":"40","author":"Savage","year":"1995","journal-title":"Arch. Oral Biol."},{"key":"ref_39","first-page":"279","article-title":"DC-SIGN and immunoregulation","volume":"3","author":"Zhou","year":"2006","journal-title":"Cell Mol. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/jid.2011.9","article-title":"Tumor-associated macrophages in the cutaneous SCC microenvironment are heterogeneously activated","volume":"131","author":"Pettersen","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7532","DOI":"10.7150\/thno.77528","article-title":"Signatures of EMT, immunosuppression, and inflammation in primary and recurrent human cutaneous squamous cell carcinoma at single-cell resolution","volume":"12","author":"Li","year":"2022","journal-title":"Theranostics"},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.eururo.2005.03.031","article-title":"Infiltration of activated dendritic cells and T cells in renal cell carcinoma following combined cytokine immunotherapy","volume":"48","author":"Verra","year":"2005","journal-title":"Eur. Urol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.ajpath.2011.03.011","article-title":"Human renal cell carcinoma induces a dendritic cell subset that uses T-cell crosstalk for tumor-permissive milieu alterations","volume":"179","author":"Figel","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Diop, M.K., Molina, O.E., Birlea, M., LaRue, H., Hovington, H., T\u00eatu, B., Lacombe, L., Bergeron, A., Fradet, Y., and Trudel, D. (2023). Leukocytic Infiltration of Intraductal Carcinoma of the Prostate: An Exploratory Study. Cancers, 15.","DOI":"10.3390\/cancers15082217"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Szpor, J., Streb, J., Glajcar, A., Fr\u0105czek, P., Winiarska, A., Tyrak, K.E., 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_47","doi-asserted-by":"crossref","unstructured":"Gylstorff, S., Wilke, V., Kraft, D., Bertrand, J., Pech, M., Haag, F., and Relja, B. (2023). Selective Internal Radiotherapy Alters the Profiles of Systemic Extracellular Vesicles in Hepatocellular Carcinoma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512512"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"714","DOI":"10.2478\/pjs-2013-0109","article-title":"Evaluation of immature monocyte-derived dendritic cells generated from patients with colorectal cancer","volume":"85","author":"Maciejewski","year":"2013","journal-title":"Pol Przegl Chir."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/1348-0421.13095","article-title":"Expression of macrophage\/dendritic cell-related molecules in lymph node sinus macrophages","volume":"67","author":"Yamada","year":"2023","journal-title":"Microbiol. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3960\/jslrt.24001","article-title":"Age-associated reduction of sinus macrophages in human mesenteric lymph nodes","volume":"64","author":"Kanemitsu","year":"2024","journal-title":"J. Clin. Exp. Hematop."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12763\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:40:58Z","timestamp":1760114458000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,27]]},"references-count":50,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252312763"],"URL":"https:\/\/doi.org\/10.3390\/ijms252312763","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,27]]}}}