CXC chemokine receptor 3 and CC chemokine receptor 4 expression in T-cell and NK-cell lymphomas with special reference to clinicopathological significance for peripheral T-cell lymphoma, unspecified

Clin Cancer Res. 2004 Aug 15;10(16):5494-500. doi: 10.1158/1078-0432.CCR-04-0371.

Abstract

We recently reported expression of the chemokine receptors CXC chemokine receptor 3 (CXCR3) and CC chemokine receptor 4 (CCR4) in adult T-cell leukemia/lymphoma and showed a preferential expression of CCR4 and its association with an unfavorable outcome. In the present study, we extend our adult T-cell leukemia/lymphoma study to other subtypes of T- and NK-cell lymphoma, to clarify whether a characteristic chemokine receptor expression pattern is obtained for each of the subtypes defined by the WHO classification. CXCR3 and CCR4 were rarely expressed in three well-defined subtypes, precursor T-lymphoblastic lymphoma, anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, and extranodal NK/T-cell lymphoma. A CXCR3-dominant expression pattern was observed in angioimmunoblastic T-cell lymphoma, while a CCR4-dominant expression pattern was observed in mycosis fungoides in transformation and in anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. CXCR3 and CCR4 were heterogeneously expressed in peripheral T-cell lymphomas, unspecified (PTCLU). We next focused on PTCLU and analyzed the clinical significance of the chemokine receptors and their association with FoxP3, a hallmark of immunoregulatory T (Treg) cells. Multivariate analysis showed that CCR4 expression was an independent and significant unfavorable prognostic factor (P < 0.001). A significant correlation was found between mRNA expression of CCR4 and FoxP3, suggesting a possible association of CCR4-positive tumors with Treg cells and thereby with an immunocompromised state. Chemokine receptors may be useful not only for further characterization of the T- and NK-cell lymphomas but also in predicting clinical outcomes for patients. We suggest that a specific therapy targeting the CCR4 molecule may be developed as an alternative treatment for patients with CCR4-positive tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Female
  • Forkhead Transcription Factors
  • Humans
  • Immunohistochemistry
  • Killer Cells, Natural / immunology*
  • Lymph Nodes / immunology
  • Lymphoma / genetics*
  • Lymphoma / immunology
  • Lymphoma / pathology
  • Lymphoma, T-Cell / genetics
  • Lymphoma, T-Cell / immunology*
  • Lymphoma, T-Cell / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymerase Chain Reaction / methods
  • Receptors, CCR3
  • Receptors, CXCR3
  • Receptors, Chemokine / analysis
  • Receptors, Chemokine / genetics*

Substances

  • CCR3 protein, human
  • CXCR3 protein, human
  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Receptors, CCR3
  • Receptors, CXCR3
  • Receptors, Chemokine