TY - JOUR
T1 - PD-L1-specific helper T-cells exhibit effective antitumor responses
T2 - New strategy of cancer immunotherapy targeting PD-L1 in head and neck squamous cell carcinoma
AU - Hirata-Nozaki, Yui
AU - Ohkuri, Takayuki
AU - Ohara, Kenzo
AU - Kumai, Takumi
AU - Nagata, Marino
AU - Harabuchi, Shohei
AU - Kosaka, Akemi
AU - Nagato, Toshihiro
AU - Ishibashi, Kei
AU - Oikawa, Kensuke
AU - Aoki, Naoko
AU - Ohara, Mizuho
AU - Harabuchi, Yasuaki
AU - Uno, Yuji
AU - Takei, Hidehiro
AU - Celis, Esteban
AU - Kobayashi, Hiroya
N1 - Publisher Copyright:
© 2019 The Author(s).
PY - 2019/6/20
Y1 - 2019/6/20
N2 - 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.
AB - 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.
KW - Cancer immunotherapy
KW - Head and neck squamous cell carcinoma
KW - Helper T-cells
KW - PD-L1
KW - Tumor-associated antigen
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U2 - 10.1186/s12967-019-1957-5
DO - 10.1186/s12967-019-1957-5
M3 - Article
C2 - 31221178
AN - SCOPUS:85067544152
SN - 1479-5876
VL - 17
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
IS - 1
M1 - 207
ER -