PD-L1-specific helper T-cells exhibit effective antitumor responses: New strategy of cancer immunotherapy targeting PD-L1 in head and neck squamous cell carcinoma

Yui Hirata-Nozaki, Takayuki Ohkuri, Kenzo Ohara, Takumi Kumai, Marino Nagata, Shohei Harabuchi, Akemi Kosaka, Toshihiro Nagato, Kei Ishibashi, Kensuke Oikawa, Naoko Aoki, Mizuho Ohara, Yasuaki Harabuchi, Yuji Uno, Hidehiro Takei, Esteban Celis, Hiroya Kobayashi

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: Head and neck squamous cell carcinoma (HNSCC) originates from squamous epithelium of the upper aerodigestive tract and is the most common malignancy in the head and neck region. Among HNSCCs, oropharynx squamous cell carcinoma (OSCC) has a unique profile and is associated with human papillomavirus infection. Recently, anti-programmed cell death-1 monoclonal antibody has yielded good clinical responses in recurrent and/or metastatic HNSCC patients. Therefore, programmed death-ligand 1 (PD-L1) may be a favorable target molecule for cancer immunotherapy. Although PD-L1-expressing malignant cells could be targeted by PD-L1-specific CD8+ cytotoxic T lymphocytes, it remains unclear whether CD4+ helper T lymphocytes (HTLs) recognize and kill tumor cells in a PD-L1-specific manner. Methods: The expression levels of PD-L1 and HLA-DR were evaluated using immunohistochemical analyses. MHC class II-binding peptides for PD-L1 were designed based on computer algorithm analyses and added into in vitro culture of HTLs with antigen-presenting cells to evaluate their stimulatory activity. Results: We found that seven of 24 cases of OSCC showed positive for both PD-L1 and HLA-DR and that PD-L1241-265 peptide efficiently activates HTLs, which showed not only cytokine production but also cytotoxicity against tumor cells in a PD-L1-dependent manner. Also, an adoptive transfer of the PD-L1-specific HTLs significantly inhibited growth of PD-L1-expressing human tumor cell lines in an immunodeficient mouse model. Importantly, T cell responses specific for the PD-L1241-265 peptide were detected in the HNSCC patients. Conclusions: The cancer immunotherapy targeting PD-L1 as a helper T-cell antigen would be a rational strategy for HNSCC patients.

Original languageEnglish (US)
Article number207
JournalJournal of Translational Medicine
Issue number1
StatePublished - Jun 20 2019


  • Cancer immunotherapy
  • Head and neck squamous cell carcinoma
  • Helper T-cells
  • PD-L1
  • Tumor-associated antigen

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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