Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of chemokines within tumors can be used to recruit immature dendritic cells (DCs) for the initiation of antitumor T-cell responses. Here, we describe the chemokine receptor expression on murine bone marrow-derived immature DCs. On the basis of these receptor studies, we chose to express the chemokines CCL3 (Mip-1alpha) or CCL20 (Mip-3alpha) in tumors. We show that expression of these chemokines in the colorectal tumor model CMT93 significantly decreases tumorigenesis. This decrease is associated with an increase in CD8 T cells, natural killer cells, and Class II DCs in the tumor within the first 24 h. Furthermore, studies in immunodeficient mice show that both natural killer cells and T cells are required for this decrease in immunogenicity. CCL3 and CCL20 expression alone did not significantly inhibit the development of the B16 melanoma tumor. However, coexpression of the Herpes Simplex Virus thymidine kinase gene (HSVtk) and CCL20, cured large established tumors where HSVtk expression alone was not sufficient. Finally, coexpression of HSVtk with either CCL3 or CCL20 was able to significantly increase protection against subsequent tumor rechallenge.
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PMID:Expression of inflammatory chemokines combined with local tumor destruction enhances tumor regression and long-term immunity. 1450 Mar 87

The first step in the generation of tumor immunity is the migration of dendritic cells (DCs) to the apoptotic tumor, which is presumed to be mediated by various chemokines. To clarify the roles of chemokines, we induced apoptosis using suicide gene therapy and investigated the immune responses following tumor apoptosis. We injected mice with a murine hepatoma cell line, BNL 1ME A.7R.1 (BNL), transfected with HSV-thymidine kinase (tk) gene and then treated the animals with ganciclovir (GCV). GCV treatment induced massive tumor cell apoptosis accompanied with intratumoral DC infiltration. Tumor-infiltrating DCs expressed chemokine receptors CCR1 and CCR5, and T cells and macrophages expressed CCL3, a ligand for CCR1 and CCR5. Moreover, tumor apoptosis increased the numbers of DCs migrating into the draining lymph nodes and eventually generated a specific cytotoxic cell population against BNL cells. Although GCV completely eradicated HSV-tk-transfected BNL cells in CCR1-, CCR5-, or CCL3-deficient mice, intratumoral and intranodal DC infiltration and the subsequent cytotoxicity generation were attenuated in these mice. When parental cells were injected again after complete eradication of primary tumors by GCV treatment, the wild-type mice completely rejected the rechallenged cells, but the deficient mice exhibited impairment in rejection. Thus, we provide definitive evidence indicating that CCR1 and CCR5 and their ligand CCL3 play a crucial role in the regulation of intratumoral DC accumulation and the subsequent establishment of tumor immunity following induction of tumor apoptosis by suicide genes.
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PMID:Tumor cell apoptosis induces tumor-specific immunity in a CC chemokine receptor 1- and 5-dependent manner in mice. 2942 58