Inhibition of adaptive immunity by IL9 can be disrupted to achieve rapid t-cell sensitization and rejection of progressive tumor challenges

Dominique B. Hoelzinger, Ana Lucia Dominguez, Peter A. Cohen, Sra J. Gendler

Research output: Contribution to journalArticle

26 Scopus citations

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 bene fits 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.

Original languageEnglish (US)
Pages (from-to)6845-6855
Number of pages11
JournalCancer research
Volume74
Issue number23
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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