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Involvement of CCR4 in tumor and its clinical significance
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Abstract:
CCR4, a member of CCR (CC chemokine receptor) family, is expressed in many kinds of lymphocytes. Its high affinity ligands include thymus, activation regulated chemokine (TARC/CCL17) and macrophagederived chemokine (MDC/CCL22/STCP1). CCR4 exerts its immune activities by CCR4＋Treg cells and CCR4+Th2 cells. High expression of CCR4 is associated with infiltration and prognosis of many hematological and solid malignancies; the binding of CCR4 with its ligands TARC and MDC in Treg cells may be responsible for the chemotaxis of Treg cells, the resulting immune tolerance and worse clinical outcomes. The researches of malignant tumor metastatic models further revealed the relationship between CCR4 expression and metastasis of malignant solid tumors. The study of KW0761, a defucosylated humanized antiCCR4 antibody,has already been in the phase Ⅱ clinical trial. Therefore, blockage TARC/MDCCCR4 signal pathway might be a novel therapy strategy for malignant tumors.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No.30570695), and the National Key Science Research Program of China (No.2006CB910501)
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