Favorable prognosis of renal cell carcinoma with increased expression of chemokines associated with a Th1-type immune response

Cancer Sci. 2006 Aug;97(8):780-6. doi: 10.1111/j.1349-7006.2006.00231.x.


The potential role of chemokines in clinical tumors remains poorly understood. Recent investigations have shown the differential expression of chemokine receptors on lymphocytes mediating Th1- and Th2-type immune responses. We examined Th1- and Th2-associated cytokines and chemokines, as well as the expression of their receptors in tumor-infiltrating lymphocytes in renal cell carcinoma (RCC). Sixty-seven patients with sporadic RCC were analyzed for the expression of Th1- and Th2-associated genes using real-time polymerase chain reaction. Tumor infiltration by CXC chemokine receptor 3 (CXCR3)-positive and CC chemokine receptor 5 (CCR5)-positive cells was detected by immunohistochemistry and by flow cytometry. The expression of Th1-associated genes was significantly increased in tumors compared to normal kidney tissues. The expression of interferon-gamma correlated positively with that of Th1 chemokines. Tumors expressing higher Th1 chemokines did not recur after curative surgery. Multivariate analysis showed that increased monokine induced by interferon (IFN)-gamma (MIG) expression was an independent favorable prognostic factor. Immunohistochemistry showed that the degree of CXCR3-positive cell infiltration significantly correlated with IFN-gamma inducible protein 10, MIG and IFN-gamma-inducible T cell a chemoattractant expression (I-TAC). Flow cytometric analysis showed increased expression of CXCR3 and CCR5 in tumor-infiltrating T lymphocytes compared to that in peripheral blood T cells. These results suggest that upregulation of the Th1-type immune response in RCC tumors with a favorable prognosis may be mediated by Th1-associated chemokines. Integrity of the Th1-type immune response seems to be required for tumor regression, suggesting that detection and correction of a defect in the Th1-type response cascade would thus be one of the main targets for tailor-made immunotherapy and gene therapy in RCC.

MeSH terms

  • Aged
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / immunology*
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Chemokines / genetics*
  • Chemokines, CXC / genetics
  • Cytokines / genetics
  • Female
  • Gene Expression
  • Humans
  • Interferon-gamma / genetics
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / immunology*
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, CXCR3
  • Receptors, CXCR5
  • Receptors, Chemokine / analysis
  • Receptors, Cytokine / analysis
  • Th1 Cells / chemistry
  • Th1 Cells / immunology*
  • Th2 Cells / chemistry
  • Th2 Cells / immunology


  • CXCL10 protein, human
  • CXCL11 protein, human
  • CXCL9 protein, human
  • CXCR3 protein, human
  • CXCR5 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Chemokines
  • Chemokines, CXC
  • Cytokines
  • RNA, Messenger
  • Receptors, CXCR3
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Interferon-gamma