title: Inhibition of adaptive immunity by IL9 can be disrupted to achieve rapid T-cell sensitization and rejection of progressive tumor challenges.
abstract: The tolerogenic cytokine IL9 promotes T regulatory cell function and allergic airway inflammation, but it has not been extensively studied in cancer. In this report, we used IL9-deficient mice to investigate the effects of IL9 in multiple models of breast and colon cancer development. Eliminating endogenous IL9 enabled sensitization of host T cells to tumors, leading to their early rejection without the requirement of vaccines or immunomodulatory therapies. Notably, IL9-deficient mice acquired immunologic memory, which actively protected from residual disease and tumor rechallenge, an effect linked to activation of CD8(+) T cells. Depletion of either CD8(+) or CD4(+) T cells abolished the benefits of IL9 loss to tumor control. Adoptive transfer experiments showed that T cells from tumor-rejecting IL9-deficient mice retained their effector competency in wild-type animals. Moreover, neutralizing IL9 antibody phenocopied the effects of IL9 gene deletion by slowing tumor progression in wild-type animals. Our results show the ability of IL9 to function as an inhibitor of adaptive immunity that prevents the formation of immunologic memory to a growing tumor, highlighting the potential for IL9 neutralization as a unique tool for cancer immunotherapy.
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, Arizona. hoelzinger.dominique@mayo.edu.
authors.forename: Dominique B
authors.initials: DB
authors.lastname: Hoelzinger
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, Arizona.
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Dominguez
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, Arizona. Department of Hematology/Oncology, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, Arizona.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Cohen
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, Arizona. Department of Hematology/Oncology, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, Arizona. Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, Arizona.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Gendler
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016906:Interleukin-9 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic
chemical_list: D016906:Interleukin-9