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Cancer Immunol Immunother. 2017 Nov;66(11):1485-1496. doi: 10.1007/s00262-017-2043-6. Epub 2017 Jul 21.

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

Author information

1
Department of Clinical Oncology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
2
Department of Clinical Oncology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. hidekazu.shirota.e1@tohoku.ac.jp.

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.

KEYWORDS:

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

PMID:
28733709
DOI:
10.1007/s00262-017-2043-6
[Indexed for MEDLINE]

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