RRC ID 45493
Author Kumai T, Ohkuri T, Nagato T, Matsuda Y, Oikawa K, Aoki N, Kimura S, Celis E, Harabuchi Y, Kobayashi H.
Title Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma.
Journal 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.
Volume 5
Pages 16280
Published 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
Times Cited 6
Human and Animal Cells HSC-3(RCB1975) HSC-4(RCB1902) Sa3(RCB0980) LU65(RCB1967)