Expression of the interferon-inducible chemokine IP-10 (CXCL10), a chemokine with proposed anti-neoplastic functions, in Hodgkin lymphoma and nasopharyngeal carcinoma

J Pathol. 2005 May;206(1):68-75. doi: 10.1002/path.1745.

Abstract

Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC) are characterized by their association with Epstein-Barr virus (EBV) and an abundant infiltrate of reactive lymphoid cells. The presence of this lymphoid stroma may influence the effect of anti-viral immunotherapy. The interferon-inducible chemokine IP-10 has anti-neoplastic effects in several model systems mediated by T-cells expressing the CXCR3 chemokine receptor. Using in situ hybridization, it is shown that IP-10 is expressed in neoplastic cells of HL and correlates both with the mixed cellularity histotype and with EBV infection. IP-10 expression was also detected in tumour cells of most NPCs as well as in EBV-negative squamous cell carcinomas of the tongue. Thus, in carcinomas, IP-10 expression showed no correlation with EBV infection. Numerous CXCR3-positive lymphocytes were detected in the lymphoid stroma of HL and NPC, raising the possibility of a Th1-predominant immune response in these cases. In view of the proposed anti-neoplastic functions of IP-10 and CXCR3-positive lymphocytes, these findings are unexpected and raise the possibility that endogenous IP-10 expression in the context of human tumours may not exert the anti-tumour effects ascribed to it by in vitro experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / immunology*
  • Carcinoma / virology
  • Carcinoma, Squamous Cell / immunology
  • Case-Control Studies
  • Cell Line, Tumor
  • Chemokine CXCL10
  • Chemokines, CXC / analysis*
  • Chemokines, CXC / immunology
  • Colonic Neoplasms / immunology
  • Epstein-Barr Virus Infections / immunology
  • Herpesvirus 4, Human
  • Hodgkin Disease / immunology*
  • Hodgkin Disease / virology
  • Humans
  • Immunohistochemistry / methods
  • In Situ Hybridization
  • Mice
  • Mice, Nude
  • Nasopharyngeal Neoplasms / immunology*
  • Nasopharyngeal Neoplasms / virology
  • Neoplasms, Experimental
  • RNA, Messenger / analysis
  • Receptors, CXCR3
  • Receptors, Chemokine / analysis
  • Receptors, Chemokine / genetics
  • Tongue Neoplasms / immunology
  • Viral Matrix Proteins / analysis
  • Viral Matrix Proteins / genetics

Substances

  • CXCR3 protein, human
  • Chemokine CXCL10
  • Chemokines, CXC
  • Cxcr3 protein, mouse
  • EBV-associated membrane antigen, Epstein-Barr virus
  • RNA, Messenger
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Viral Matrix Proteins