Regression of a mammary adenocarcinoma in STAT6-/- mice is dependent on the presence of STAT6-reactive T cells.

Abstract

Polarization of the immune response toward a type 1 cytokine profile has been posited to be associated with a therapeutic antitumor immune response. STAT6-/- mice are unable to generate a type 2 immune response, and instead mount an enhanced type 1 response. STAT6-/- mice are significantly more resistant to 4T1, a mammary adenocarcinoma cell line, resisting a 10-fold higher tumor dose compared with wild-type (wt) BALB/c mice. An analysis of the T cells from tumor-bearing STAT6-/- mice revealed that they contained a population primed by a peptide (STAT6(531-539)) of the STAT6 protein expressed in 4T1. The adoptive transfer of T cells from STAT6(531-539)-vaccinated STAT6-/- mice significantly reduced the number of 4T1 pulmonary metastases in recipient mice. Additionally, the role of these STAT6(531-539)-reactive T cells against s.c. 4T1 tumor challenge was determined by tumor-challenging wt BALB/c mice reconstituted with STAT6-/- bone marrow, thereby assessing whether a polarized type 1 immune response in the absence of STAT6-reactive T cells was sufficient to reject a 4T1 tumor challenge. T cells from the STAT6-/- bone marrow chimeras failed to recognize the STAT6(531-539), and these mice proved to be as susceptible as wt BALB/c mice to 4T1 challenge. This demonstrated that the absence of STAT6(531-539)-reactive T cells correlated with the inability to reject 4T1 challenge. Additionally, these data emphasize that the enhanced ability to mount a type 1-polarized immune response is inconsequential if a sufficient antitumor immune response is not primed by the tumor.

• Authors: Shawn M Jensen, Sybren L Meijer, Robert A Kurt, Walter J Urba, Hong-Ming Hu, Bernard A Fox
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 170 Issue 4 Pg. 2014-21 (Feb 15 2003) ISSN: 0022-1767 [Print] United States
• PMID: 12574371 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cancer Vaccines
• Peptide Fragments
• STAT6 Transcription Factor
• Stat6 protein, mouse
• Trans-Activators

Topics

• Adenocarcinoma (genetics, immunology, metabolism, therapy)
• Adoptive Transfer
• Animals
• Cancer Vaccines (administration & dosage, immunology)
• Female
• Graft Rejection (genetics, immunology)
• Injections, Subcutaneous
• Mammary Neoplasms, Experimental (genetics, immunology, metabolism, prevention & control)
• Melanoma, Experimental
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Neoplasm Transplantation
• Peptide Fragments (administration & dosage, immunology, metabolism)
• STAT6 Transcription Factor
• T-Lymphocyte Subsets (immunology, metabolism, transplantation)
• Th1 Cells (immunology, metabolism)
• Trans-Activators (administration & dosage, biosynthesis, deficiency, genetics)
• Tumor Cells, Cultured (transplantation)