{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:38:55Z","timestamp":1775018335494,"version":"3.50.1"},"reference-count":64,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5906,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Chemotactic cytokines (chemokines) play an important role in the recruitment of lymphocytes to tissue by regulating cellular adhesion and transendothelial migration. This study examined the expression and function of CXC (human monokine induced by \u03b3-interferon [HuMig], interleukin-8 [IL-8], and interferon-inducible protein-10 [IP-10]) and CC (macrophage inflammatory protein-1\u03b1 [MIP-1\u03b1], MIP-1\u03b2, regulated upon activation normal T lymphocyte expressed and secreted (RANTES), and macrophage chemoattractant protein-1 [MCP-1]) chemokines and their respective receptors on lymphocytes infiltrating human liver tumors. Chemokine and chemokine receptor expression was assessed by immunohistochemistry, flow cytometry, <jats:italic toggle=\"yes\">in situ<\/jats:italic> hybridization and ribonuclease (RNAse) protection assays and function by <jats:italic toggle=\"yes\">in vitro<\/jats:italic> chemotaxis of tumor-derived lymphocytes to purified chemokines and to HepG2 tumor cell culture supernatants. Tumor-derived lymphocytes showed strong chemotactic responses to both CC and CXC chemokines <jats:italic toggle=\"yes\">in vitro<\/jats:italic> and expressed high levels of CXCR3 (HuMig and IP-10 receptor) and CCR5 (RANTES, MIP-1\u03b1, and MIP-1\u03b2 receptor). Expansion of tumor-derived lymphocytes in recombinant IL-2 increased expression of CXCR3. The corresponding chemokines were detected on vascular endothelium (HuMig, IL-8, MIP-1\u03b1, and MIP-1\u03b2) and sinusoidal endothelium (HuMig, MIP-1\u03b1, MIP-1\u03b2) in hepatocellular carcinoma. <jats:italic toggle=\"yes\">In vitro,<\/jats:italic> HepG2 cells secreted functional chemotactic factors for tumor-derived lymphocytes that could be inhibited using anti-CCR5 or anti-CXCR3 monoclonal antibodies (MoAbs). Thus, lymphocytes infiltrating human liver tumors express receptors for and respond to both CXC and CC chemokines. The relevant chemokine ligands are expressed in hepatocellular carcinoma (HCC), particularly HuMig, which was strongly expressed by tumor endothelium, suggesting that they play a role in lymphocyte recruitment to these tumors <jats:italic toggle=\"yes\">in vivo<\/jats:italic>. The ability of HepG2 cells to secrete lymphocyte chemotactic factors <jats:italic toggle=\"yes\">in vitro<\/jats:italic> suggests that the tumor contributes to lymphocyte recruitment <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510300147","type":"journal-article","created":{"date-parts":[[2004,7,28]],"date-time":"2004-07-28T07:26:03Z","timestamp":1090999563000},"page":"100-111","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":110,"title":["Expression and function of CXC and CC chemokines in human malignant liver tumors: A role for human monokine induced by \u03b3-interferon in lymphocyte recruitment to hepatocellular carcinoma"],"prefix":"10.1097","volume":"30","author":[{"given":"Khong F.","family":"Yoong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon C.","family":"Afford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pav","family":"Aujla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shixin","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate","family":"Price","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan G.","family":"Hubscher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"BIB1","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/S0952-7915(96)80078-1","volume":"8","author":"Robbins","year":"1996","journal-title":"Curr Opin Immunol"},{"key":"BIB2","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.4049\/jimmunol.154.5.2257","volume":"154","author":"Rivoltini","year":"1995","journal-title":"J Immunol"},{"key":"BIB3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0022-1759(91)90345-G","volume":"139","author":"Yannelli","year":"1991","journal-title":"J Immunol Methods"},{"key":"BIB4","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1126\/science.1840703","volume":"2","author":"van der Bruggen","year":"1991","journal-title":"Science"},{"key":"BIB5","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1073\/pnas.94.5.1914","volume":"94","author":"Chen","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"key":"BIB6","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/jnci\/86.15.1159","volume":"86","author":"Rosenberg","year":"1994","journal-title":"J Natl Cancer Inst"},{"key":"BIB7","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1097\/00002371-199411000-00009","volume":"16","author":"Escudier","year":"1994","journal-title":"J Immunother"},{"key":"BIB8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/00002371-199402000-00002","volume":"15","author":"Finke","year":"1994","journal-title":"J Immunother"},{"key":"BIB9","first-page":"522","volume":"110","author":"McNab","year":"1996","journal-title":"A mechanism for T cell recirculation to the liver? 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