Migration of cytotoxic T lymphocytes toward melanoma cells in three‐dimensional organotypic culture is dependent on CCL2 and CCR4

Studies in experimental animal models have demonstrated that chemokines produced by tumor cells attract chemokine receptor‐positive T lymphocytes into the tumor area. However, in cancer patients, the role of chemokines in T lymphocyte trafficking toward human tumor cells is relatively unexplored. In...

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Bibliographic Details
Published in:European Journal of Immunology 2006-02, Vol.36 (2), p.457-467
Main Authors: Zhang, Tianqian, Somasundaram, Rajasekharan, Berencsi, Klara, Caputo, Laura, Gimotty, Phyllis, Rani, Pyapalli, Guerry, DuPont, Swoboda, Rolf, Herlyn, Dorothee
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - pharmacology
Apoptosis - drug effects
Apoptosis - immunology
Cell Culture Techniques
Chemokine CCL2 - immunology
Chemokine CCL2 - therapeutic use
Chemokines
Chemotaxis
Chemotaxis - drug effects
Chemotaxis - immunology
CTL
Female
Humans
Melanoma - drug therapy
Melanoma - immunology
Melanoma - pathology
Mice
Receptors, CCR4
Receptors, Chemokine - immunology
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - pathology
Tumor apoptosis
Tumor Cells, Cultured
Tumor immunity
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Summary:Studies in experimental animal models have demonstrated that chemokines produced by tumor cells attract chemokine receptor‐positive T lymphocytes into the tumor area. However, in cancer patients, the role of chemokines in T lymphocyte trafficking toward human tumor cells is relatively unexplored. In the present study, the migration of a melanoma patient's CTL toward autologous tumor cells has been studied in a novel three‐dimensional organotypic melanoma culture. In this model, CTL migrated toward tumor cells, resulting in tumor cell apoptosis. CTL migration was mediated by the CC chemokine receptor (CCR)4 expressed by the CTL and the CC chemokine ligand (CCL)2 secreted by the tumor cells, as evidenced by blockage of CTL migration by CCL2 or antibodies to CCL2 or CCR4. These results were confirmed in a Transwell migration assay in which the CTL actively migrated toward isolated CCL2 and migration was inhibited by anti‐CCR4 antibody. These studies, together with previous studies in mice indicating regression of CCL2‐transduced tumor cells, suggest that CCL2 may be useful as an immunotherapeutic agent for cancer patients.
ISSN:0014-2980
1521-4141
1365-2567
DOI:10.1002/eji.200526208