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Tumor immunity : a balancing act between T cell activation, macrophage activation and tumor-induced immune suppression

The mouse 4T1 mammary carcinoma is a BALB/c-derived tumor that spontaneously metastasizes and induces immune suppression. Although >95% of wild type BALB/c mice die from metastatic 4T1 tumor even if the primary mammary tumor is surgically removed, >65% of BALB/c mice with a deleted Signal Tran...

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Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2005-11, Vol.54 (11), p.1137-1142
Main Authors: SINHA, Pratima, CLEMENTS, Virginia K, MILLER, Seth, OSTRAND-ROSENBERG, Suzanne
Format: Article
Language:English
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Summary:The mouse 4T1 mammary carcinoma is a BALB/c-derived tumor that spontaneously metastasizes and induces immune suppression. Although >95% of wild type BALB/c mice die from metastatic 4T1 tumor even if the primary mammary tumor is surgically removed, >65% of BALB/c mice with a deleted Signal Transducer Activator of Transcription 6 (STAT6) gene survive post-surgery. STAT6-deficiency also confers enhanced immunity against spontaneously developing breast cancer since NeuT+/- mice that are STAT6-deficient develop mammary tumors later and survive longer than NeuT+/- mice that are STAT6-competent. Rejection of metastastic disease and survival of STAT6-deficient mice after removal of primary tumor involve three mechanisms: (1) The generation of M1 type macrophages that produce nitric oxide and are tumoricidal; (2) A decrease to normal in the elevated levels of myeloid suppressor cells that accumulate during primary tumor growth; and (3) CD8+ tumor-specific T lymphocytes. STAT6-deficient, but not wild type BALB/c, mice generate nitric oxide producing macrophages because they lack the STAT6 transcription factor which is necessary for signaling through the type 2 IL-4Ralpha complex, and which induces the production of arginase instead of nitric oxide.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-005-0703-4