Cancer Immunology, Immunotherapy

, Volume 54, Issue 11, pp 1137–1142

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

  • Pratima Sinha
  • Virginia K. Clements
  • Seth Miller
  • Suzanne Ostrand-Rosenberg
Symposium Paper

DOI: 10.1007/s00262-005-0703-4

Cite this article as:
Sinha, P., Clements, V.K., Miller, S. et al. Cancer Immunol Immunother (2005) 54: 1137. doi:10.1007/s00262-005-0703-4

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.

Keywords

Tumor-induced immune suppressionImmune surveillanceM1 macrophagesMetastatic breast cancerCell-mediated tumor immunity

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Pratima Sinha
    • 1
  • Virginia K. Clements
    • 1
  • Seth Miller
    • 1
  • Suzanne Ostrand-Rosenberg
    • 1
  1. 1.Department of Biological SciencesUniversity of Maryland Baltimore CountyBaltimoreUSA