, Volume 54, Issue 11, pp 1137-1142

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

Purchase on Springer.com

$39.95 / €34.95 / £29.95*

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

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-4Rα complex, and which induces the production of arginase instead of nitric oxide.

This article is a symposium paper from the conference “Tumor Escape and Its Determinants”, held in Salzburg, Austria, on 10–13 October 2004