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http://ir.nhri.org.tw/handle/3990099045/13682
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| Title: | Sharpening up tumor microenvironment to enhance the efficacy of immune checkpoint blockade on head and neck cancer using a CpG-oligodeoxynucleotide |
| Authors: | Tseng, JC;Yang, JX;Liu, YL;Su, YW;Lee, AY;Chen, YW;Liu, KJ;Luo, Y;Hong, YR;Chuang, TH |
| Contributors: | Immunology Research Center;National Institute of Cancer Research |
| Abstract: | Head and neck cancers are a type of life-threatening cancers characterized by an immunosuppressive tumor microenvironment. Only less than 20% of the patients respond to immune checkpoint blockade therapy, indicating the need for a strategy to increase the efficacy of immunotherapy for this type of cancers. Previously, we identified a type B CpG-oligodeoxynucleotide (CpG-ODN) called CpG-2722, which has the universal activity of eliciting an immune response in grouper, mouse, and human cells. In this study, we further characterized and compared its cytokine-inducing profiles with different types of CpG-ODNs. The antitumor effect of CpG-2722 was further investigated alone and in combination with an immune checkpoint inhibitor in a newly developed syngeneic orthotopic head and neck cancer animal model. Along with other inflammatory cytokines, CpG-2722 induces the gene expressions of interleukin-12 and different types of interferons, which are critical for the antitumor response. Both CpG-2722 and anti-programmed death (PD)-1 alone suppressed tumor growth. Their tumor suppression efficacies were further enhanced when CpG-2722 and anti-PD-1 were used in combination. Mechanistically, CpG-2722 shaped a tumor microenvironment that is favorable for the action of anti-PD-1, which included promoting the expression of different cytokines such as IL-12, IFN-β, and IFN-γ, and increasing the presence of plasmacytoid dendritic cells, M1 macrophages, and CD8 positive T cells. Overall, CpG-2722 provided a priming effect for CD8 positive T cells by sharpening the tumor microenvironment, whereas anti-PD-1 released the brake for their tumor-killing effect, resulting in an enhanced efficacy of the combined CpG-2722 and anti-PD-1. |
| Date: | 2022-05 |
| Relation: | Cancer Immunology, Immunotherapy. 2022 May;71(5):1115-1128. |
| Link to: | http://dx.doi.org/10.1007/s00262-021-03062-8 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0340-7004&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000701644300001 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85115840929 |
| Appears in Collections: | [莊宗顯] 期刊論文
[蘇郁文] 期刊論文
[劉柯俊] 期刊論文
[陳雅雯] 期刊論文
[李岳倫] 期刊論文
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| PUB34581869.pdf | | 1960Kb | Adobe PDF | 245 | View/Open |
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