title: 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.affiliation: Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, 4805 NE Glisan Street, Portland, OR 97213, USA.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Jensen
authors.forename: Sybren L
authors.initials: SL
authors.lastname: Meijer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kurt
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
authors.forename: Hong-Ming
authors.initials: HM
authors.lastname: Hu
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Fox
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D019264:Adoptive Transfer; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D007279:Injections, Subcutaneous; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D008546:Melanoma, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D050800:STAT6 Transcription Factor; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000008:administration & dosage / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000637:transplantation
chemical_list: D019496:Cancer Vaccines; D010446:Peptide Fragments; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators