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Article: Desensitization of T lymphocyte function by CXCR3 ligands in human hepatocellular carcinoma

TitleDesensitization of T lymphocyte function by CXCR3 ligands in human hepatocellular carcinoma
Authors
KeywordsCXCR3 ligands
Hepatocellular carcinoma
Issue Date2005
PublisherBaishideng Publishing Group. The Journal's web site is located at http://www.wjgnet.com/1007-9327/index.htm
Citation
World Journal Of Gastroenterology, 2005, v. 11 n. 2, p. 164-170 How to Cite?
AbstractAim: Despite the presence of lymphocyte infiltration, human hepatocellular carcinoma (HCC) is typically a rapidly progressive disease. The mechanism of regulation of lymphocyte migration is poorly understood. In this study, we investigated various factors regulating T cell migration in HCC patients. We examined serum CXC chemokine levels in HCC patients and demonstrated the production of CXC chemokines by HCC cell lines. We determined the effect of both HCC patient serum and tumor cell conditioned supernatant upon lymphocyte expression of chemokine receptor CXCR3 as well as lymphocyte migration. Lastly, we examined the chemotactic responses of lymphocytes derived from HCC patients. Methods: The serum chemokines IP-10 (CXCL10) and Mig (CXCL9) levels were measured by cytometric bead array (CBA) and the tumor tissue IP-10 concentration was measured by ELISA. The surface expression of CXCR3 on lymphocytes was determined by flow cytometry. The migratory function of lymphocytes to the corresponding chemokines was assessed using an in vitro chemotactic assay. Phosphorylation of extracellular signal-regulated kinase (ERK) was determined by Western blot analysis. Results: Increased levels of IP-10 and Mig were detected in HCC patient serum and culture supernatants of HCC cell lines. The IP-10 concentration in the tumor was significantly higher than that in the non-involved adjacent liver tissues. HCC cell lines secreted functional chemokines that induced a CXCR3-specific chemotactic response of lymphocytes. Furthermore, tumor-cell-derived chemokines induced initial rapid phosphorylation of lymphocyte ERK followed by later inhibition of ERK phosphorylation. The culture of normal lymphocytes with HCC cell line supernatants or medium containing serum from HCC patients resulted in a significant reduction in the proportion of lymphocytes exhibiting surface expression of CXCR3. The reduction in T cell expression of CXCR3 resulted in reduced migration toward the ligand IP-10, and both CD4 + and CD8 + T cells from HCC patients exhibited diminished chemotactic responses to IP-10 in vitro compared to T cells from healthy control subjects. Conclusion: This study demonstrates functional desensitization of the chemokine receptor CXCR3 in lymphocytes from HCC patients by CXCR3 ligands secreted by tumor cells. This may cause lymphocyte dysfunction and subsequently impaired immune defense against the tumor. © 2005 The WJG Press and Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/83452
ISSN
2023 Impact Factor: 4.3
2023 SCImago Journal Rankings: 1.063
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLiu, YQen_HK
dc.contributor.authorPoon, RTen_HK
dc.contributor.authorHughes, Jen_HK
dc.contributor.authorLi, QYen_HK
dc.contributor.authorYu, WCen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-06T08:41:12Z-
dc.date.available2010-09-06T08:41:12Z-
dc.date.issued2005en_HK
dc.identifier.citationWorld Journal Of Gastroenterology, 2005, v. 11 n. 2, p. 164-170en_HK
dc.identifier.issn1007-9327en_HK
dc.identifier.urihttp://hdl.handle.net/10722/83452-
dc.description.abstractAim: Despite the presence of lymphocyte infiltration, human hepatocellular carcinoma (HCC) is typically a rapidly progressive disease. The mechanism of regulation of lymphocyte migration is poorly understood. In this study, we investigated various factors regulating T cell migration in HCC patients. We examined serum CXC chemokine levels in HCC patients and demonstrated the production of CXC chemokines by HCC cell lines. We determined the effect of both HCC patient serum and tumor cell conditioned supernatant upon lymphocyte expression of chemokine receptor CXCR3 as well as lymphocyte migration. Lastly, we examined the chemotactic responses of lymphocytes derived from HCC patients. Methods: The serum chemokines IP-10 (CXCL10) and Mig (CXCL9) levels were measured by cytometric bead array (CBA) and the tumor tissue IP-10 concentration was measured by ELISA. The surface expression of CXCR3 on lymphocytes was determined by flow cytometry. The migratory function of lymphocytes to the corresponding chemokines was assessed using an in vitro chemotactic assay. Phosphorylation of extracellular signal-regulated kinase (ERK) was determined by Western blot analysis. Results: Increased levels of IP-10 and Mig were detected in HCC patient serum and culture supernatants of HCC cell lines. The IP-10 concentration in the tumor was significantly higher than that in the non-involved adjacent liver tissues. HCC cell lines secreted functional chemokines that induced a CXCR3-specific chemotactic response of lymphocytes. Furthermore, tumor-cell-derived chemokines induced initial rapid phosphorylation of lymphocyte ERK followed by later inhibition of ERK phosphorylation. The culture of normal lymphocytes with HCC cell line supernatants or medium containing serum from HCC patients resulted in a significant reduction in the proportion of lymphocytes exhibiting surface expression of CXCR3. The reduction in T cell expression of CXCR3 resulted in reduced migration toward the ligand IP-10, and both CD4 + and CD8 + T cells from HCC patients exhibited diminished chemotactic responses to IP-10 in vitro compared to T cells from healthy control subjects. Conclusion: This study demonstrates functional desensitization of the chemokine receptor CXCR3 in lymphocytes from HCC patients by CXCR3 ligands secreted by tumor cells. This may cause lymphocyte dysfunction and subsequently impaired immune defense against the tumor. © 2005 The WJG Press and Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherBaishideng Publishing Group. The Journal's web site is located at http://www.wjgnet.com/1007-9327/index.htmen_HK
dc.relation.ispartofWorld Journal of Gastroenterologyen_HK
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCXCR3 ligandsen_HK
dc.subjectHepatocellular carcinomaen_HK
dc.titleDesensitization of T lymphocyte function by CXCR3 ligands in human hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1007-9327&volume=11&issue=2&spage=164&epage=170&date=2005&atitle=Desensitization+of+T+lymphocyte+function+by+CXCR3+ligands+in+human+hepatocellular+carcinomaen_HK
dc.identifier.emailPoon, RT: poontp@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityPoon, RT=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3748/wjg.v11.i2.164-
dc.identifier.pmid15633209-
dc.identifier.pmcidPMC4205395-
dc.identifier.scopuseid_2-s2.0-12344292438en_HK
dc.identifier.hkuros96959en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-12344292438&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume11en_HK
dc.identifier.issue2en_HK
dc.identifier.spage164en_HK
dc.identifier.epage170en_HK
dc.identifier.isiWOS:000208098500002-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLiu, YQ=14627533300en_HK
dc.identifier.scopusauthoridPoon, RT=7103097223en_HK
dc.identifier.scopusauthoridHughes, J=7404719934en_HK
dc.identifier.scopusauthoridLi, QY=8639537800en_HK
dc.identifier.scopusauthoridYu, WC=37022285400en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.issnl1007-9327-

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