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

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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.

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Abbreviations

Arg 1:

Arginase 1

CFSE:

Carboxyfluorescein succinimidyl ester

EGF:

Epidermal growth factor

GZMB:

Granzyme B

IFNg:

IFN-gamma

MDSC:

Myeloid-derived suppressor cells

NOS2:

Nitric oxide synthase 2

ODN:

Oligodeoxynucleotides

TAM:

Tumor-associated macrophages

Tfh cells:

T follicular helper cells

Treg cell:

Regulatory T cell

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Clinical Oncology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan

    Shuku-ei Ito, Hidekazu Shirota, Yuki Kasahara, Ken Saijo & Chikashi Ishioka

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  1. Shuku-ei Ito
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  2. Hidekazu Shirota
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  3. Yuki Kasahara
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  4. Ken Saijo
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  5. Chikashi Ishioka
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Correspondence to Hidekazu Shirota.

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Funding

This work was supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) KAKENHI Grant No. 25430103 and 16K07106, Japan.

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Ito, Se., Shirota, H., Kasahara, Y. et al. IL-4 blockade alters the tumor microenvironment and augments the response to cancer immunotherapy in a mouse model. Cancer Immunol Immunother 66, 1485–1496 (2017). https://doi.org/10.1007/s00262-017-2043-6

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  • DOI: https://doi.org/10.1007/s00262-017-2043-6

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