Cited 47 times in
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 | 민병소 | - |
dc.contributor.author | 신상준 | - |
dc.contributor.author | 한윤대 | - |
dc.date.accessioned | 2018-11-16T16:52:25Z | - |
dc.date.available | 2018-11-16T16:52:25Z | - |
dc.date.issued | 2018 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/165417 | - |
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 α-galactosylceramide (αGC) 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 αGC 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 αGC-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. Cancer Res; 78(18); 5315-26. ©2018 AACR. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isPartOf | CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | 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.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Surgery (외과학교실) | - |
dc.contributor.googleauthor | Eun-Ah Bae | - |
dc.contributor.googleauthor | Hyungseok Seo | - |
dc.contributor.googleauthor | Byung-Seok Kim | - |
dc.contributor.googleauthor | Jeongwon Choi | - |
dc.contributor.googleauthor | Insu Jeon | - |
dc.contributor.googleauthor | Kwang-Soo Shin | - |
dc.contributor.googleauthor | Choong-Hyun Koh | - |
dc.contributor.googleauthor | Boyeong Song | - |
dc.contributor.googleauthor | Il-Kyu Kim | - |
dc.contributor.googleauthor | Byung Soh Min | - |
dc.contributor.googleauthor | Yoon Dae Han | - |
dc.contributor.googleauthor | Sang Joon Shin | - |
dc.contributor.googleauthor | Chang-Yuil Kang | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-18-0734 | - |
dc.contributor.localId | A01402 | - |
dc.contributor.localId | A02105 | - |
dc.contributor.localId | A04313 | - |
dc.relation.journalcode | J00452 | - |
dc.identifier.eissn | 1538-7445 | - |
dc.identifier.pmid | 30012672 | - |
dc.identifier.url | http://cancerres.aacrjournals.org/content/78/18/5315.long | - |
dc.contributor.alternativeName | Min, Byung Soh | - |
dc.contributor.alternativeName | Shin, Sang Joon | - |
dc.contributor.alternativeName | Han, Yoon Dae | - |
dc.contributor.affiliatedAuthor | 민병소 | - |
dc.contributor.affiliatedAuthor | 신상준 | - |
dc.contributor.affiliatedAuthor | 한윤대 | - |
dc.citation.volume | 78 | - |
dc.citation.number | 18 | - |
dc.citation.startPage | 5315 | - |
dc.citation.endPage | 5326 | - |
dc.identifier.bibliographicCitation | CANCER RESEARCH, Vol.78(18) : 5315-5326, 2018 | - |
dc.identifier.rimsid | 58882 | - |
dc.type.rims | ART | - |
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