{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:46:45Z","timestamp":1791607605506,"version":"4.3.4"},"reference-count":115,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T00:00:00Z","timestamp":1595376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chemokines, which are basic proteins that exert their effects via G protein-coupled receptors and a subset of the cytokine family, are mediators deeply involved in leukocyte migration during an inflammatory reaction. Chemokine (C-C motif) ligand 20 (CCL20), also known as macrophage inflammatory protein (MIP)-3\u03b1, liver activation regulated chemokine (LARC), and Exodus-1, is a small protein that is physiologically expressed in the liver, colon, and skin, is involved in tissue inflammation and homeostasis, and has a specific receptor C-C chemokine receptor 6 (CCR6). The CCL20-CCR6 axis has long been known to be involved in inflammatory and infectious diseases, such as rheumatoid arthritis and human immunodeficiency virus infections. Recently, however, reports have shown that the CCL20-CCR6 axis is associated with several cancers, including hepatocellular carcinoma, colorectal cancer, breast cancer, pancreatic cancer, cervical cancer, and kidney cancer. The CCL20-CCR6 axis promotes cancer progression directly by enhancing migration and proliferation of cancer cells and indirectly by remodeling the tumor microenvironment through immune cell control. The present article reviewed the role of the CCL20-CCR6 axis in cancer progression and its potential as a therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms21155186","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T10:14:06Z","timestamp":1595499246000},"page":"5186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":249,"title":["The CCL20-CCR6 Axis in Cancer Progression"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4136-8998","authenticated-orcid":false,"given":"Suguru","family":"Kadomoto","sequence":"first","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8480-9100","authenticated-orcid":false,"given":"Kouji","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Mizokami","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1084\/jem.190.10.1417","article-title":"In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas","volume":"190","author":"Bell","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"Accessories to the crime: Functions of cells recruited to the tumor microenvironment","volume":"21","author":"Hanahan","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.immuni.2012.05.008","article-title":"The chemokine superfamily revisited","volume":"36","author":"Zlotnik","year":"2012","journal-title":"Immunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1056\/NEJMra052723","article-title":"The many roles of chemokines and chemokine receptors in inflammation","volume":"354","author":"Charo","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1146\/annurev-immunol-032713-120145","article-title":"Chemokines and chemokine receptors: Positioning cells for host defense and immunity","volume":"32","author":"Griffith","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_6","first-page":"386","article-title":"Chemokines in inflammatory bowel diseases","volume":"28","author":"Atreya","year":"2010","journal-title":"Dig. Dis. (Basel Switz.)"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s10456-016-9509-6","article-title":"mTORC2 mediates CXCL12-induced angiogenesis","volume":"19","author":"Ziegler","year":"2016","journal-title":"Angiogenesis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/s12985-017-0902-6","article-title":"The CC chemokine ligand (CCL) 1, upregulated by the viral transactivator Tax, can be downregulated by minocycline: Possible implications for long-term treatment of HTLV-1-associated myelopathy\/tropical spastic paraparesis","volume":"14","author":"Saito","year":"2017","journal-title":"Virol. J."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Marcuzzi, E., Angioni, R., Molon, B., and Cali, B. (2018). Chemokines and Chemokine Receptors: Orchestrating Tumor Metastasization. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010096"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1002\/cam4.3014","article-title":"Chemokines and chemokine receptors: A new strategy for breast cancer therapy","volume":"9","author":"Liu","year":"2020","journal-title":"Cancer Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.canlet.2008.03.028","article-title":"Cancer related inflammation: The macrophage connection","volume":"267","author":"Sica","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1084\/jem.186.6.825","article-title":"Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells","volume":"186","author":"Power","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_13","first-page":"3315","article-title":"Cloning and characterization of exodus, a novel beta-chemokine","volume":"89","author":"Hromas","year":"1997","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.3892\/mmr.2015.3800","article-title":"Inflammation and oxidative stress, rather than hypoxia, are predominant factors promoting angiogenesis in the initial phases of atherosclerosis","volume":"12","author":"Xiao","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5846","DOI":"10.1074\/jbc.272.9.5846","article-title":"Molecular cloning of a novel human CC chemokine liver and activation-regulated chemokine (LARC) expressed in liver. Chemotactic activity for lymphocytes and gene localization on chromosome 2","volume":"272","author":"Hieshima","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Nandi, B., Pai, C., Huang, Q., Prabhala, R.H., Munshi, N.C., and Gold, J.S. (2014). CCR6, the sole receptor for the chemokine CCL20, promotes spontaneous intestinal tumorigenesis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097566"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1002\/1521-4141(200107)31:7<1981::AID-IMMU1981>3.0.CO;2-X","article-title":"Neutrophils produce biologically active macrophage inflammatory protein-3alpha (MIP-3alpha)\/CCL20 and MIP-3beta\/CCL19","volume":"31","author":"Scapini","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8391","DOI":"10.4049\/jimmunol.181.12.8391","article-title":"CCR6 regulates the migration of inflammatory and regulatory T cells","volume":"181","author":"Yamazaki","year":"2008","journal-title":"J. Immunol. (Baltim. Md 1950)"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14893","DOI":"10.1074\/jbc.272.23.14893","article-title":"Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC","volume":"272","author":"Baba","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S1074-7613(00)80201-0","article-title":"CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue","volume":"12","author":"Cook","year":"2000","journal-title":"Immunity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1196\/annals.1326.036","article-title":"CCR6 and CCL20: Partners in intestinal immunity and lymphorganogenesis","volume":"1072","author":"Williams","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/ni1467","article-title":"Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells","volume":"8","author":"Rivino","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1038\/bjc.2016.113","article-title":"CCR6 expression in colon cancer is associated with advanced disease and supports epithelial-to-mesenchymal transition","volume":"114","author":"Kapur","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1007\/s12094-015-1420-x","article-title":"CCR6 overexpression predicted advanced biological behaviors and poor prognosis in patients with gastric cancer","volume":"18","author":"Zhang","year":"2016","journal-title":"Clin. Transl. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1084\/jem.20070663","article-title":"Phenotypic and functional features of human Th17 cells","volume":"204","author":"Annunziato","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/eji.200636251","article-title":"Functional expression of chemokine receptor CCR6 on human effector memory CD8+ T cells","volume":"37","author":"Kondo","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.imbio.2019.01.005","article-title":"The CCR6-CCL20 axis in humoral immunity and T-B cell immunobiology","volume":"224","author":"Lee","year":"2019","journal-title":"Immunobiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1158\/1078-0432.CCR-14-1860","article-title":"Immune escape mechanisms as a guide for cancer immunotherapy","volume":"21","author":"Beatty","year":"2015","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the tumor immune microenvironment (TIME) for effective therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.cell.2017.01.018","article-title":"Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future","volume":"168","author":"McGranahan","year":"2017","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1158\/0008-5472.CAN-16-1383","article-title":"Heterogeneous Stromal Signaling within the Tumor Microenvironment Controls the Metastasis of Pancreatic Cancer","volume":"77","author":"Rucki","year":"2017","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8831","DOI":"10.3748\/wjg.v19.i47.8831","article-title":"Hierarchical and selective roles of galectins in hepatocarcinogenesis, liver fibrosis and inflammation of hepatocellular carcinoma","volume":"19","author":"Bacigalupo","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1142\/S2339547818300020","article-title":"The growing role of precision and personalized medicine for cancer treatment","volume":"6","author":"Krzyszczyk","year":"2018","journal-title":"Technology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3804","DOI":"10.1172\/JCI57099","article-title":"Breast cancer stem cells, cytokine networks, and the tumor microenvironment","volume":"121","author":"Korkaya","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nri.2017.49","article-title":"Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy","volume":"17","author":"Nagarsheth","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1007\/s11605-011-1775-4","article-title":"High expression of CCL20 is associated with poor prognosis in patients with hepatocellular carcinoma after curative resection","volume":"16","author":"Ding","year":"2012","journal-title":"J. Gastrointest. Surg. Off. J. Soc. Surg. Aliment. Tract"},{"key":"ref_37","first-page":"3977","article-title":"CCL20 is overexpressed in hepatocellular carcinoma with bile duct tumor thrombus and correlates negatively with surgical outcome","volume":"11","author":"Yang","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_38","first-page":"1151","article-title":"CCR6(+) B lymphocytes responding to tumor cell-derived CCL20 support hepatocellular carcinoma progression via enhancing angiogenesis","volume":"7","author":"He","year":"2017","journal-title":"Am. J. Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/1440-1681.12689","article-title":"A tumour-promoting role of Th9 cells in hepatocellular carcinoma through CCL20 and STAT3 pathways","volume":"44","author":"Tan","year":"2017","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9610","DOI":"10.1038\/s41598-017-09040-4","article-title":"Human antigen R-regulated CCL20 contributes to osteolytic breast cancer bone metastasis","volume":"7","author":"Lee","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chen, W., Qin, Y., Wang, D., Zhou, L., Liu, Y., Chen, S., Yin, L., Xiao, Y., Yao, X.H., and Yang, X. (2018). CCL20 triggered by chemotherapy hinders the therapeutic efficacy of breast cancer. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2005869"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1186\/s12967-019-2008-y","article-title":"Serum CCL20 combined with IL-17A as early diagnostic and prognostic biomarkers for human colorectal cancer","volume":"17","author":"Wang","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/s40425-019-0701-2","article-title":"Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1\/CEBPB\/NF-kappaB signaling","volume":"7","author":"Wang","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.bbamcr.2017.02.005","article-title":"Role of CCL20 mediated immune cell recruitment in NF-kappaB mediated TRAIL resistance of pancreatic cancer","volume":"1864","author":"Geismann","year":"2017","journal-title":"Biochim. Et Biophys. Acta Mol. Cell Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1093\/abbs\/gmw101","article-title":"Tumor-associated macrophage-derived CCL20 enhances the growth and metastasis of pancreatic cancer","volume":"48","author":"Liu","year":"2016","journal-title":"Acta Biochim. Et Biophys. Sin."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00432-008-0403-5","article-title":"Chemokine receptor CCR6 expression level and aggressiveness of prostate cancer","volume":"134","author":"Ghadjar","year":"2008","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Beider, K., Abraham, M., Begin, M., Wald, H., Weiss, I.D., Wald, O., Pikarsky, E., Abramovitch, R., Zeira, E., and Galun, E. (2009). Interaction between CXCR4 and CCL20 pathways regulates tumor growth. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005125"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.canlet.2015.04.005","article-title":"Tobacco smoke induces production of chemokine CCL20 to promote lung cancer","volume":"363","author":"Wang","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_49","first-page":"1946","article-title":"lncRNA-u50535 promotes the progression of lung cancer by activating CCL20\/ERK signaling","volume":"42","author":"Wei","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_50","first-page":"8183","article-title":"Role of CCL20\/CCR6 and the ERK signaling pathway in lung adenocarcinoma","volume":"14","author":"Zhang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e0120855","DOI":"10.1371\/journal.pone.0120855","article-title":"Preferential recruitment of Th17 cells to cervical cancer via CCR6-CCL20 pathway","volume":"10","author":"Yu","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5248","DOI":"10.1158\/0008-5472.CAN-15-0732","article-title":"Stromal Fibroblasts Induce CCL20 through IL6\/C\/EBP\u03b2 to Support the Recruitment of Th17 Cells during Cervical Cancer Progression","volume":"75","author":"Mavrova","year":"2015","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.cyto.2015.05.009","article-title":"CrkL meditates CCL20\/CCR6-induced EMT in gastric cancer","volume":"76","author":"Han","year":"2015","journal-title":"Cytokine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.canlet.2019.12.024","article-title":"Cisplatin-stimulated macrophages promote ovarian cancer migration via the CCL20-CCR6 axis","volume":"472","author":"Liu","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kadomoto, S., Izumi, K., Hiratsuka, K., Nakano, T., Naito, R., Makino, T., Iwamoto, H., taegashi, H., Shigehara, K., and Kadono, Y. (2019). Tumor-Associated Macrophages Induce Migration of Renal Cell Carcinoma Cells via Activation of the CCL20-CCR6 Axis. Cancers, 12.","DOI":"10.3390\/cancers12010089"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/jcar.JCar_9_16","article-title":"Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis","volume":"16","author":"Ghouri","year":"2017","journal-title":"J. Carcinog."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S1470-2045(09)70241-4","article-title":"Management of hepatocellular carcinoma in Asia: Consensus statement from the Asian Oncology Summit 2009","volume":"10","author":"Poon","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s12072-010-9165-7","article-title":"Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma","volume":"4","author":"Omata","year":"2010","journal-title":"Hepatol. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.3748\/wjg.v16.i15.1832","article-title":"Chemokines and hepatocellular carcinoma","volume":"16","author":"Huang","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11241","DOI":"10.3748\/wjg.v20.i32.11241","article-title":"Advances in pancreatic cancer research: Moving towards early detection","volume":"20","author":"He","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e26853","DOI":"10.4161\/onci.26853","article-title":"Targeting inflammatory cytokines-androgen receptor (AR) signaling with ASC-J9(\u00ae) to better battle prostate cancer progression","volume":"2","author":"Izumi","year":"2013","journal-title":"Oncoimmunology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1002\/emmm.201202367","article-title":"Targeting the androgen receptor with siRNA promotes prostate cancer metastasis through enhanced macrophage recruitment via CCL2\/CCR2-induced STAT3 activation","volume":"5","author":"Izumi","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nrc798","article-title":"Papillomaviruses and cancer: From basic studies to clinical application","volume":"2","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.3816\/CGC.2008.s.002","article-title":"Current algorithms and prognostic factors in the treatment of metastatic renal cell carcinoma","volume":"6","author":"Molina","year":"2008","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1148\/rg.266065010","article-title":"Common and uncommon histologic subtypes of renal cell carcinoma: Imaging spectrum with pathologic correlation","volume":"26","author":"Prasad","year":"2006","journal-title":"Radiographics"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4961","DOI":"10.21873\/anticanres.11064","article-title":"Treatment Outcome of Low-dose Interleukin-2 Therapy in Patients with Metastatic Renal Cell Carcinoma","volume":"36","author":"Takezawa","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1056\/NEJMoa1712126","article-title":"Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma","volume":"378","author":"Motzer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"51525","DOI":"10.18632\/oncotarget.10492","article-title":"CCL2\/CCR2 axis is associated with postoperative survival and recurrence of patients with non-metastatic clear-cell renal cell carcinoma","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/ijc.25981","article-title":"Osteoblast-secreted factors enhance the expression of dysadherin and CCL2-dependent migration of renal carcinoma cells","volume":"130","author":"Geiger","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1002\/cam4.886","article-title":"CCL2 as a potential therapeutic target for clear cell renal cell carcinoma","volume":"5","author":"Arakaki","year":"2016","journal-title":"Cancer Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6384","DOI":"10.4049\/jimmunol.181.9.6384","article-title":"CCL3-CCR5 axis regulates intratumoral accumulation of leukocytes and fibroblasts and promotes angiogenesis in murine lung metastasis process","volume":"181","author":"Wu","year":"2008","journal-title":"J. Immunol. (Baltim. Md: 1950)"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1172\/JCI82976","article-title":"A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer","volume":"127","author":"Berlato","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"45525","DOI":"10.18632\/oncotarget.9997","article-title":"C-met inhibition blocks bone metastasis development induced by renal cancer stem cells","volume":"7","author":"Belisario","year":"2016","journal-title":"Oncotarget"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Middel, P., Brauneck, S., Meyer, W., and Radzun, H.J. (2010). Chemokine-mediated distribution of dendritic cell subsets in renal cell carcinoma. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-578"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.eururo.2011.10.035","article-title":"T lymphocyte recruitment into renal cell carcinoma tissue: A role for chemokine receptors CXCR3, CXCR6, CCR5, and CCR6","volume":"61","author":"Oldham","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.coi.2005.11.008","article-title":"The mononuclear phagocyte system","volume":"18","author":"Hume","year":"2006","journal-title":"Curr. Opin. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/ni.2705","article-title":"Tissue-resident macrophages","volume":"14","author":"Davies","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"514","DOI":"10.3389\/fimmu.2014.00514","article-title":"From Monocytes to M1\/M2 Macrophages: Phenotypical vs. Functional Differentiation","volume":"5","author":"Italiani","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7230","DOI":"10.1158\/1078-0432.CCR-11-1354","article-title":"Tumor-associated macrophages promote angiogenesis and melanoma growth via adrenomedullin in a paracrine and autocrine manner","volume":"17","author":"Chen","year":"2011","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/S1470-2045(18)30700-9","article-title":"Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial","volume":"19","author":"Hodi","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1158\/2326-6066.CIR-17-0198","article-title":"CCL20 Expression by Tumor-Associated Macrophages Predicts Progression of Human Primary Cutaneous Melanoma","volume":"6","author":"Samaniego","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e1189052","DOI":"10.1080\/2162402X.2016.1189052","article-title":"Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages","volume":"5","author":"Nandi","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Chen, K.J., Lin, S.Z., Zhou, L., Xie, H.Y., Zhou, W.H., Taki-Eldin, A., and Zheng, S.S. (2011). Selective recruitment of regulatory T cell through CCR6-CCL20 in hepatocellular carcinoma fosters tumor progression and predicts poor prognosis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024671"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Liu, J., Zhang, N., Li, Q., Zhang, W., Ke, F., Leng, Q., Wang, H., Chen, J., and Wang, H. (2011). Tumor-associated macrophages recruit CCR6+ regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019495"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1007\/s00262-007-0318-z","article-title":"Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival","volume":"56","author":"Griffiths","year":"2007","journal-title":"Cancer Immunol. Immunother. CII"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/ni1254","article-title":"Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages","volume":"6","author":"Harrington","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nri2742","article-title":"T(H)17 cells in tumour immunity and immunotherapy","volume":"10","author":"Zou","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1146\/annurev.immunol.021908.132710","article-title":"IL-17 and Th17 Cells","volume":"27","author":"Korn","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.4049\/jimmunol.0902813","article-title":"Tumor microenvironments direct the recruitment and expansion of human Th17 cells","volume":"184","author":"Su","year":"2010","journal-title":"J. Immunol. (Baltim. Md 1950)"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.humimm.2012.07.333","article-title":"Chemokine\/chemokine receptor interactions contribute to the accumulation of Th17 cells in patients with esophageal squamous cell carcinoma","volume":"73","author":"Chen","year":"2012","journal-title":"Hum. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1158\/1078-0432.CCR-07-5164","article-title":"Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing","volume":"14","author":"Sfanos","year":"2008","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.jhep.2008.12.033","article-title":"Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients","volume":"50","author":"Zhang","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1158\/0008-5472.CAN-10-2907","article-title":"Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer","volume":"71","author":"Tosolini","year":"2011","journal-title":"Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1136\/gutjnl-2015-310016","article-title":"Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer","volume":"66","author":"Amicarella","year":"2017","journal-title":"Gut"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"947","DOI":"10.3892\/mmr.2014.2778","article-title":"Skewed T-helper (Th)1\/2- and Th17\/T regulatory-cell balances in patients with renal cell carcinoma","volume":"11","author":"Li","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"947","DOI":"10.17219\/acem\/70065","article-title":"Myeloid-derived suppressor cell accumulation in renal cell carcinoma is correlated with CCL2, IL-17 and IL-18 expression in blood and tumors","volume":"27","author":"Guan","year":"2018","journal-title":"Adv. Clin. Exp. Med. Off. Organ Wroc. Med Univ."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1182\/blood.V92.11.4150","article-title":"Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo","volume":"92","author":"Gabrilovich","year":"1998","journal-title":"Blood"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1158\/0008-5472.CAN-06-3037","article-title":"The terminology issue for myeloid-derived suppressor cells","volume":"67","author":"Gabrilovich","year":"2007","journal-title":"Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/2326-6066.CIR-16-0297","article-title":"Myeloid-Derived Suppressor Cells","volume":"5","author":"Gabrilovich","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.it.2016.01.004","article-title":"The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment","volume":"37","author":"Kumar","year":"2016","journal-title":"Trends Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1084\/jem.20100587","article-title":"HIF-1\u03b1 regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment","volume":"207","author":"Corzo","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1073\/pnas.1113744109","article-title":"Origins of tumor-associated macrophages and neutrophils","volume":"109","author":"Etzrodt","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.canlet.2006.12.012","article-title":"CCL2\/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers","volume":"252","author":"Huang","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.celrep.2015.06.024","article-title":"CCL2 Promotes Colorectal Carcinogenesis by Enhancing Polymorphonuclear Myeloid-Derived Suppressor Cell Population and Function","volume":"12","author":"Chun","year":"2015","journal-title":"Cell Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1593\/neo.07307","article-title":"CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration","volume":"9","author":"Loberg","year":"2007","journal-title":"Neoplasia (NY)"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1158\/1078-0432.CCR-15-1823","article-title":"Myeloid-Derived Suppressor Cell Subset Accumulation in Renal Cell Carcinoma Parenchyma Is Associated with Intratumoral Expression of IL1\u03b2, IL8, CXCL5, and Mip-1\u03b1","volume":"23","author":"Najjar","year":"2017","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1111\/bcp.13286","article-title":"CCL20 neutralization by a monoclonal antibody in healthy subjects selectively inhibits recruitment of CCR6(+) cells in an experimental suction blister","volume":"83","author":"Bouma","year":"2017","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Robert, R., Juglair, L., Lim, E.X., Ang, C., Wang, C.J.H., Ebert, G., Dolezal, O., and Mackay, C.R. (2017). A fully humanized IgG-like bispecific antibody for effective dual targeting of CXCR3 and CCR6. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184278"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.jaci.2019.07.013","article-title":"Oral Janus kinase\/SYK inhibition (ASN002) suppresses inflammation and improves epidermal barrier markers in patients with atopic dermatitis","volume":"144","author":"Pavel","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.canlet.2014.03.008","article-title":"CCL20 and CXCL8 synergize to promote progression and poor survival outcome in patients with colorectal cancer by collaborative induction of the epithelial-mesenchymal transition","volume":"348","author":"Cheng","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1080\/14397595.2017.1416923","article-title":"The ROR\u03b3t-CCR6-CCL20 axis augments Th17 cells invasion into the synovia of rheumatoid arthritis patients","volume":"28","author":"Kaneko","year":"2018","journal-title":"Mod. Rheumatol."},{"key":"ref_114","first-page":"109","article-title":"IL-17 secreted by tumor reactive T cells induces IL-8 release by human renal cancer cells","volume":"32","author":"Inozume","year":"2009","journal-title":"J. Immunother. (Hagerstown Md 1997)"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/path.5267","article-title":"IL-8 and CXCR1 expression is associated with cancer stem cell-like properties of clear cell renal cancer","volume":"248","author":"Healy","year":"2019","journal-title":"J. Pathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5186\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:50:43Z","timestamp":1760176243000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,22]]},"references-count":115,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ijms21155186"],"URL":"https:\/\/doi.org\/10.3390\/ijms21155186","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,22]]}}}