Cancer Science · 2006 · 95 citations · 22 references
MedicineImmunologyOncologyCancer ImmunologyTumor ImmunologyTumor MicroenvironmentChemokine SignalingCytokines In Tumor ImmunityImmune Cell InfiltrationKidney CancerRenal Cell CarcinomaTumor-infiltrating LymphocytesChemokines In Tumor MicroenvironmentChemokines In Tumor ProgressionCytokine Signaling In TumorsG Protein-coupled Chemokine ReceptorsRenal Cell Carcinoma BiomarkersTumor Immune Cell InfiltrationTumor Infiltration AssessmentTumor-associated Cytokines
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.
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Raffaella Bonecchi, Paola Panina‐Bordignon, Daniele D’Ambrosio et al. · The Journal of Experimental Medicine · 1998 · 2K citations · Full text
A new class of membrane-bound chemokine with a CX3C motif
J. Fernando Bazán, Kevin B. Bacon, Gary Hardiman et al. · Nature · 1997 · 2K citations