| RRC ID |
45493
|
| 著者 |
Kumai T, Ohkuri T, Nagato T, Matsuda Y, Oikawa K, Aoki N, Kimura S, Celis E, Harabuchi Y, Kobayashi H.
|
| タイトル |
Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma.
|
| ジャーナル |
Sci Rep
|
| Abstract |
HER-3 expression has been reported to act as an important oncoprotein in head and neck squamous cell carcinoma. This protein is known to control tumor proliferation and acquisition of resistance by tumor cells towards EGFR inhibitors, therefore, development of a HER-3-targeted therapy is desirable. In this study, we found that HER-3 expression on tumor cells was increased after EGFR inhibition. To establish a novel therapeutic approach for HER-3-positive head and neck carcinoma, we identified a HER-3 helper epitope that could elicit effective helper T cell responses to the naturally processed HER-3-derived epitope presented in a HER-3 expressing tumors. This epitope induced potent cytolytic activity of CD4 T cells against such tumor cells. Moreover, pan HER-family tyrosine kinase inhibitor augmented the responses of HER-3-reactive CD4 T cells via upregulation of HLA-DR protein on the surface of tumor cells. Our results supports the validity of CD4 T cell-dependent HER-3-targeted therapy combined with a broad inhibitor of HER-family.
|
| 巻・号 |
5
|
| ページ |
16280
|
| 公開日 |
2015-11-5
|
| DOI |
10.1038/srep16280
|
| PII |
srep16280
|
| PMID |
26538233
|
| PMC |
PMC4633732
|
| MeSH |
Animals
CD4-Positive T-Lymphocytes / drug effects
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
Carcinoma, Squamous Cell / drug therapy*
Carcinoma, Squamous Cell / immunology
Carcinoma, Squamous Cell / metabolism
Cell Line
Cell Line, Tumor
Epitopes, T-Lymphocyte / drug effects
Epitopes, T-Lymphocyte / immunology
Epitopes, T-Lymphocyte / metabolism
ErbB Receptors / metabolism
HLA-DR Antigens / metabolism
Head and Neck Neoplasms / drug therapy*
Head and Neck Neoplasms / immunology
Head and Neck Neoplasms / metabolism
Humans
Jurkat Cells
Lymphocyte Activation / drug effects
Lymphocyte Activation / immunology
Mice
Protein Kinase Inhibitors / pharmacology*
Receptor, ErbB-3 / metabolism*
T-Lymphocytes, Helper-Inducer / drug effects*
T-Lymphocytes, Helper-Inducer / immunology
T-Lymphocytes, Helper-Inducer / metabolism
Up-Regulation / drug effects
|
| IF |
3.998
|
| 引用数 |
6
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HSC-3(RCB1975)
HSC-4(RCB1902)
Sa3(RCB0980)
LU65(RCB1967) |
