c-Met is a novel tumor associated antigen for T-cell based immunotherapy against NK/T cell lymphoma

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

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: The expression of c-Met and its ligand HGF plays a critical role in cell proliferation and is involved in numerous malignancies. Because c-Met expression and its role in NK/T-cell lymphoma remain unclear, we studied the expression and function of c-Met in NK/T-cell lymphoma cells. In addition, we investigated the possibility that c-Met could function as a tumor-associated antigen for helper T lymphocytes (HTLs). Methods: We evaluated whether HGF and c-Met were expressed in NK/T-cell lymphoma and the capacity of predicted c-Met HTL epitopes to induce antitumor responses in vitro. In addition, c-Met inhibitor was evaluated for the ability to inhibit TGF-β production in tumor and subsequently increase HTL recognition. Results: c-Met and HGF were expressed in NK/T-cell lymphoma cell lines, nasal NK/T-cell lymphoma specimens and patient serum samples. Moreover, HGF was shown to promote NK/T cell lymphoma (NKTCL) proliferation in an autocrine manner. Furthermore, we have identified three novel c-Met HTL epitopes that were restricted by several HLADR molecules. Notably, peptide-induced HTL lines directly recognized and killed c-Met expressing NK/T-cell lymphomas and various epithelial solid tumors. The c-Met specific HTLs could also recognize dendritic cells (DCs) pulsed with c-Met expressing tumor cell lysates. In addition, we observed that c-Met inhibition augmented HTL recognition by decreasing TGF-β production by tumor cells. Lastly, autophagy partly regulated the HTL responses against tumors. Conclusions: We identified novel c-Met HTL epitopes that can elicit effective antitumor responses against tumors expressing c-Met. Our results provide the rationale of combining c-Met targeting therapy and immunotherapy for NKTCLs and epithelial tumors.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalOncoImmunology
Volume4
Issue number2
DOIs
StatePublished - 2015

Keywords

  • Autophagy
  • C-Met
  • CD4 helper T lymphocytes
  • Head and neck squamous cell carcinoma
  • Immunotherapy
  • Major histo-compatibility complex class II
  • NK/T cell lymphoma
  • TGF-β
  • Tumor antigens

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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