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Activation of NKT cells in an anti-PD-1-resistant tumor model enhances antitumor immunity by reinvigorating exhausted CD8 T cells : Activation of NKT Cells in an Anti-PD-1-Resistant Tumor Model Enhances Antitumor Immunity by Reinvigorating Exhausted CD8 T Cells
DC Field | Value | Language |
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dc.contributor.author | Bae, Eun-Ah | - |
dc.contributor.author | Seo, Hyungseok | - |
dc.contributor.author | Kim, Byung-Seok | - |
dc.contributor.author | Choi, Jeongwon | - |
dc.contributor.author | Jeon, Insu | - |
dc.contributor.author | Shin, Kwang-Soo | - |
dc.contributor.author | Koh, Choong-Hyun | - |
dc.contributor.author | Song, Boyeong | - |
dc.contributor.author | Kim, Il-Kyu | - |
dc.contributor.author | Min, Byung Soh | - |
dc.contributor.author | Han, Yoon Dae | - |
dc.contributor.author | Shin, Sang Joon | - |
dc.contributor.author | Kang, Chang-Yuil | - |
dc.date.accessioned | 2023-05-08T08:25:38Z | - |
dc.date.available | 2023-05-08T08:25:38Z | - |
dc.date.created | 2019-06-25 | - |
dc.date.created | 2019-06-25 | - |
dc.date.created | 2019-06-25 | - |
dc.date.created | 2019-06-25 | - |
dc.date.created | 2019-06-25 | - |
dc.date.issued | 2018-09 | - |
dc.identifier.citation | Cancer Research, Vol.78 No.18, pp.5315-5326 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://hdl.handle.net/10371/192155 | - |
dc.description.abstract | PD-1-based cancer immunotherapy is a successful example of immune checkpoint blockade that provides long-term durable therapeutic effects in patients with cancer across a wide spectrum of cancer types. Accumulating evidence suggests that anti-PD-1 therapy enhances antitumor immunity by reversing the function of exhausted T cells in the tumor environment. However, the responsiveness rate of patients with cancer to anti-PD-1 therapy remains low, providing an urgent need for optimization and improvement. In this study, we designed an anti-PD-1-resistant mouse tumor model and showed that unresponsiveness to anti-PD-1 is associated with a gradual increase in CD8 T-cell exhaustion. We also found that invariant natural killer T cell stimulation by the synthetic ligand alpha-galactosylceramide (alpha GC) can enhance the antitumor effect in anti-PD-1-resistant tumors by restoring the effector function of tumor antigen-specific exhausted CD8 T cells. IL2 and IL12 were among the cytokines produced by alpha GC stimulation critical for reinvigorating exhausted CD8 T cells in tumor-bearing mice and patients with cancer. Furthermore, we observed a synergistic increase in the antitumor effect between alpha GC-loaded antigen-presenting cells and PD-1 blockade in a therapeutic murine tumor model. Our study suggests NKT cell stimulation as a promising therapeutic strategy for the treatment of patients with anti-PD-1-resistant cancer. Significance: These findings provide mechanistic insights into the application of NKT cell stimulation as a potent adjuvant for immunotherapy against advanced cancer. (C) 2018 AACR. | - |
dc.language | 영어 | - |
dc.publisher | American Association for Cancer Research | - |
dc.title | Activation of NKT cells in an anti-PD-1-resistant tumor model enhances antitumor immunity by reinvigorating exhausted CD8 T cells | - |
dc.title.alternative | Activation of NKT Cells in an Anti-PD-1-Resistant Tumor Model Enhances Antitumor Immunity by Reinvigorating Exhausted CD8 T Cells | - |
dc.type | Article | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-18-0734 | - |
dc.citation.journaltitle | Cancer Research | - |
dc.identifier.wosid | 000444803700011 | - |
dc.identifier.scopusid | 2-s2.0-85053219196 | - |
dc.citation.endpage | 5326 | - |
dc.citation.number | 18 | - |
dc.citation.startpage | 5315 | - |
dc.citation.volume | 78 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Seo, Hyungseok | - |
dc.contributor.affiliatedAuthor | Kang, Chang-Yuil | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ANTIGEN-PRESENTING CELLS | - |
dc.subject.keywordPlus | CHRONIC VIRAL-INFECTION | - |
dc.subject.keywordPlus | B-CELLS | - |
dc.subject.keywordPlus | CANCER-IMMUNOTHERAPY | - |
dc.subject.keywordPlus | IL-12 PRODUCTION | - |
dc.subject.keywordPlus | IFN-GAMMA | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | BLOCKADE | - |
dc.subject.keywordPlus | LIGAND | - |
dc.subject.keywordPlus | PD-1 | - |
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