期刊
ONCOIMMUNOLOGY
卷 5, 期 6, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2016.1169356
关键词
Human leukocyte antigen G; immune escape; immunotherapy; peptide vaccine; 5-aza-2 '-deoxycytidine
资金
- JSPS KAKENHI Grant [24791735]
- National Cancer Institute of the National Institutes of Health [R01CA136828, R01CA157303]
- Augusta University Cancer Center
- Georgia Research Alliance
- Grants-in-Aid for Scientific Research [24791735] Funding Source: KAKEN
Tumor immune escape has been a major problem for developing effective immunotherapy. The human leukocyte antigen G (HLA-G) is a non-classical MHC class I molecule whose primary function is to protect the fetus from the mother's immune system. While HLA-G is hardly found in normal adult tissues, various tumor cells are known to express it, aiding their escape from the immune system. Thus, HLA-G is an attractive immunotherapy target. CD4(+) helper T lymphocytes (HTLs) play an important role in the immune reaction against tumors by assisting in the generation and persistence of CD8(+) cytotoxic T lymphocytes (CTLs) or by displaying direct antitumor effects. We report here that HLA-G expression in breast cancer significantly correlates with a poor prognosis. Also, we describe that the MHC class II-binding peptide HLA-G(26-40) was effective in eliciting tumor-reactive CD4(+) T cell responses. Furthermore, treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine increased HLA-G expression in tumors and subsequently enhanced recognition by HLA-G(26-40)-specific HTLs. These findings predict that a combination immunotherapy targeting HLA-G together with a DNA methyltransferase inhibitor could be useful against some cancers.
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