期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 66, 期 11, 页码 1485-1496出版社
SPRINGER
DOI: 10.1007/s00262-017-2043-6
关键词
IL-4; Macrophages; CD8; CpG ODN; Anti-OX40 Ab
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan [25430103, 16K07106]
- Grants-in-Aid for Scientific Research [25430103, 16K07106] Funding Source: KAKEN
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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