期刊
JOURNAL OF IMMUNOLOGY
卷 179, 期 5, 页码 3332-3341出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.5.3332
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资金
- NCI NIH HHS [R01 CA 103959, 5P30 CA 33572-01] Funding Source: Medline
To exert a therapeutic effect, adoptively transferred tumor-specific CTLs must traffic to sites of tumor burden, exit the circulation, and infiltrate the tumor microenvironment. In this study, we examine the ability of adoptively transferred human CTL to traffic to tumors with disparate chemokine secretion profiles independent of tumor Ag recognition. Using a combination of in vivo tumor tropism studies and in vitro biophotonic chemotaxis assays, we observed that cell lines derived from glioma, medulloblastoma, and renal cell carcinoma efficiently chemoattracted ex vivo-expanded primary human T cells. We compared the chemokines secreted by tumor cell lines with high chernotactic activity with those that failed to elicit T cell chemotaxis (Daudi lymphoma, 10HTB neuroblastoma, and A2058 melanoma cells) and found a correlation between tumorderived production of MCP-1/CCL2 ( >= 10 ng/ml) and T cell chemotaxis. Chemokine immunodepletion studies confirmed that tumor-derived MCP-I elicits effector T cell chemotaxis. Moreover, MCP-I is sufficient for in vivo T cell tumor tropism as evidenced by the selective accumulation of Lv. administered firefly luciferase-expressing T cells in intracerebral xenografts of tumor transfectants secreting MCP-1. These studies suggest that the capacity of adoptively transferred T cells to home to tumors may be, in part, dictated by the species and amounts of tumor-derived chemokines, in particular MCP-1.
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