A dual role for tumor-derived chemokine RANTES (CCL5)

To investigate the role of tumor-derived CCL5 (regulated upon activation, normal T cell expressed and secreted, RANTES) in tumor immunity we compared the T cell response to tumors derived from the 4T1 murine mammary carcinoma cell line that express different levels of CCL5. Tumors that expressed low...

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Bibliographic Details
Published in:Immunology letters 2003-12, Vol.90 (2-3), p.187-194
Main Authors: Adler, Evan P., Lemken, Charles A., Katchen, Nicholas S., Kurt, Robert A.
Format: Article
Language:English
Subjects:
4T1
Animals
CCL5
Cell Division
Chemokine CCL5 - genetics
Chemokine CCL5 - metabolism
Chemotaxis
Flow Cytometry
Gene Expression Regulation, Neoplastic
Lymph Nodes - immunology
Matrix Metalloproteinase 9 - genetics
Mice
Mice, Inbred BALB C
Mice, SCID
MMP9
Neoplasm Transplantation
Neoplasms - immunology
Neoplasms - metabolism
Neoplasms - pathology
RANTES
T-Lymphocytes - cytology
T-Lymphocytes - immunology
Time Factors
Tumor Cells, Cultured
Tumor immunity
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Summary:To investigate the role of tumor-derived CCL5 (regulated upon activation, normal T cell expressed and secreted, RANTES) in tumor immunity we compared the T cell response to tumors derived from the 4T1 murine mammary carcinoma cell line that express different levels of CCL5. Tumors that expressed low levels of CCL5 exhibited a decrease in the in vivo, but not the in vitro, growth rate. In conjunction with the decreased growth rate the tumors that produced lower levels of CCL5 contained a greater number of tumor infiltrating lymphocytes compared to tumors that express normal levels of CCL5. One explanation for these findings was that a reduction in tumor-derived CCL5 prevented the tumor-associated alteration in T cell chemotactic activity. Tumors expressing lower levels of CCL5 also elicited a greater tumor-specific T cell response as evident by examination of recently activated T cells from tumor-draining lymph nodes. However, despite the enhanced T cell response, tumors expressing low levels of CCL5 still grew slower than tumors expressing normal levels of CCL5 in SCID mice. These data are consistent with the ability of CCL5 to upregulate transcription of matrix metalloproteinase-9 (MMP9), which can contribute to angiogenesis and thus, foster growth in vivo. Consequently, these data indicate that tumor-derived CCL5 can inhibit the T cell response and enhance the in vivo growth of murine mammary carcinoma.
ISSN:0165-2478
1879-0542
DOI:10.1016/j.imlet.2003.09.013