IL-4 blockade alters the tumor microenvironment and augments the response to cancer immunotherapy in a mouse model

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12 Citations (Scopus)

Abstract

Recent findings show that immune cells constitute a large fraction of the tumor microenvironment and that they modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL-4, in particular, is upregulated. Thus, we tested whether IL-4 neutralization would affect tumor immunity. Current results demonstrate that the administration of a neutralizing antibody against IL-4 enhances anti-tumor immunity and delays tumor progression. IL-4 blockade also alters inflammation in the tumor microenvironment, reducing the generation of both immunosuppressive M2 macrophages and myeloid-derived suppressor cells, and enhancing tumor-specific cytotoxic T lymphocytes. In addition, IL-4 blockade improves the response to anti-OX40 Ab or CpG oligodeoxynucleotide immunotherapies. These findings suggest that IL-4 affects anti-tumor immunity and constitutes an attractive therapeutic target to reduce immune suppression in the tumor microenvironment, thus enhancing the efficacy of cancer therapy.

Original languageEnglish
Pages (from-to)1485-1496
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume66
Issue number11
DOIs
Publication statusPublished - 2017 Nov 1

Keywords

  • Anti-OX40 Ab
  • CD8
  • CpG ODN
  • IL-4
  • Macrophages

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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