Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma

Takumi Kumai, Takayuki Ohkuri, Toshihiro Nagato, Yoshinari Matsuda, Kensuke Oikawa, Naoko Aoki, Shoji Kimura, Esteban Celis, Yasuaki Harabuchi, Hiroya Kobayashi

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number16280
JournalScientific Reports
Volume5
DOIs
StatePublished - Nov 5 2015

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Helper-Inducer T-Lymphocytes
Epitopes
Neoplasms
T-Lymphocytes
Oncogene Proteins
HLA-DR Antigens
Reproducibility of Results
Protein-Tyrosine Kinases
Carcinoma, squamous cell of head and neck
Membrane Proteins
Neck
Up-Regulation
Therapeutics
Head
Carcinoma
Proteins

ASJC Scopus subject areas

  • General

Cite this

Kumai, T., Ohkuri, T., Nagato, T., Matsuda, Y., Oikawa, K., Aoki, N., ... Kobayashi, H. (2015). Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma. Scientific Reports, 5, [16280]. https://doi.org/10.1038/srep16280

Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma. / Kumai, Takumi; Ohkuri, Takayuki; Nagato, Toshihiro; Matsuda, Yoshinari; Oikawa, Kensuke; Aoki, Naoko; Kimura, Shoji; Celis, Esteban; Harabuchi, Yasuaki; Kobayashi, Hiroya.

In: Scientific Reports, Vol. 5, 16280, 05.11.2015.

Research output: Contribution to journalArticle

Kumai, T, Ohkuri, T, Nagato, T, Matsuda, Y, Oikawa, K, Aoki, N, Kimura, S, Celis, E, Harabuchi, Y & Kobayashi, H 2015, 'Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma', Scientific Reports, vol. 5, 16280. https://doi.org/10.1038/srep16280
Kumai, Takumi ; Ohkuri, Takayuki ; Nagato, Toshihiro ; Matsuda, Yoshinari ; Oikawa, Kensuke ; Aoki, Naoko ; Kimura, Shoji ; Celis, Esteban ; Harabuchi, Yasuaki ; Kobayashi, Hiroya. / Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma. In: Scientific Reports. 2015 ; Vol. 5.
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AU - Aoki, Naoko

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