Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 36, Issue 2, Pages 457-467Publisher
WILEY
DOI: 10.1002/eji.200526208
Keywords
CTL; chemokines; chemotaxis; tumor apoptosis; tumor immunity
Categories
Funding
- NCI NIH HHS [P50 CA93372, CA25874] Funding Source: Medline
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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.
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