Cancer Immunology, Immunotherapy

, Volume 53, Issue 2, pp 86–91

Signal transducer and activator of transcription 6 (Stat6) and CD1: inhibitors of immunosurveillance against primary tumors and metastatic disease

Authors

    • Department of Biological SciencesUniversity of Maryland, Baltimore County
  • Pratima Sinha
    • Department of Biological SciencesUniversity of Maryland, Baltimore County
  • Virginia Clements
    • Department of Biological SciencesUniversity of Maryland, Baltimore County
  • Samudra I. Dissanayake
    • Department of Biological SciencesUniversity of Maryland, Baltimore County
  • Seth Miller
    • Department of Biological SciencesUniversity of Maryland, Baltimore County
  • Cordula Davis
    • Department of Biological SciencesUniversity of Maryland, Baltimore County
  • Erika Danna
    • Department of Biological SciencesUniversity of Maryland, Baltimore County
Symposium in Writing

DOI: 10.1007/s00262-003-0446-z

Cite this article as:
Ostrand-Rosenberg, S., Sinha, P., Clements, V. et al. Cancer Immunol Immunother (2004) 53: 86. doi:10.1007/s00262-003-0446-z

Abstract

Many tumor immunologists favor the hypothesis that optimal anti-tumor activity is mediated by type 1 CD4+ and CD8+ T cells, and that the production of type 2 CD4+ T cells may be counterproductive for effective anti-tumor immunity. Since Stat6-deficient or “knockout” mice lack the signal transducer and activator of transcription-6 protein and are unable to transmit signals initiated by the type 2 cytokines, IL-4 and IL-13, they have been studied to confirm the T h 1 vs T h 2 paradigm. Using transplantable tumor cells that cause primary solid tumors and metastatic disease, as well as a spontaneous transgenic tumor model, multiple studies have demonstrated that Stat6-/- mice are able to reject or delay primary tumor growth, prevent recurrence of primary tumors, and/or reject established, spontaneous metastatic disease. Deletion of the Stat6 gene, therefore, provides significantly enhanced immunosurveillance. Comparable experiments with CD1-deficient mice, which lack NKT cells and hence are deficient for IL-13, give similar results and suggest that removal of NKT cells also enhances immunosurveillance. Because immunity is enhanced in the absence of Stat6 or CD1, it has been hypothesized that these deletions result in the removal of an inhibitor that blocks constitutive immunosurveillance. Several mechanisms have been tested as potential inhibitors, including CD4+CD25+ T regulatory cells, IL-13, a T h 2 shift, and myeloid suppressor cells. Although the first three mechanisms do not appear to be relevant, regression of myeloid suppressor cells in Stat6-deficient and CD1-deficient mice may be responsible for enhanced immunosurveillance. Although additional studies are clearly needed to clarify the mechanism(s) underlying improved anti-tumor immunity in Stat6-/- and CD1-/- mice, deletion of these genes results in a potent anti-tumor immunity and may be a basis for an immunotherapy strategy.

Abbreviations

Stat6

signal transducer and activator of transcription 6

MSC

myeloid suppressor cell

BALB/c NeuT

transgenic mice that spontaneously develop mammary carcinoma

Stat6-/-NeuT+/-

Stat6-deficient, BALB/c NeuT mice

Stat6-/-IFNγ-/-

Stat6-deficient, interferon-γ-deficient BALB/c mice

Copyright information

© Springer-Verlag 2003