دورية أكاديمية
Systemic administration of a TLR7 agonist attenuates regulatory T cells by dendritic cell modification and overcomes resistance to PD-L1 blockade therapy.
| العنوان: | Systemic administration of a TLR7 agonist attenuates regulatory T cells by dendritic cell modification and overcomes resistance to PD-L1 blockade therapy. |
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| المؤلفون: | Nishii N; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.; Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Tachinami H; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Kondo Y; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Xia Y; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Kashima Y; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.; Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Ohno T; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Nagai S; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Li L; Birdie Biopharmaceuticals Inc., Iselin, NJ, USA., Lau W; Birdie Biopharmaceuticals Inc., Iselin, NJ, USA., Harada H; Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Azuma M; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. |
| المصدر: | Oncotarget [Oncotarget] 2018 Jan 27; Vol. 9 (17), pp. 13301-13312. Date of Electronic Publication: 2018 Jan 27 (Print Publication: 2018). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Impact Journals Country of Publication: United States NLM ID: 101532965 Publication Model: eCollection Cited Medium: Internet ISSN: 1949-2553 (Electronic) Linking ISSN: 19492553 NLM ISO Abbreviation: Oncotarget Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Albany, N.Y. : Impact Journals |
| مستخلص: | Research on immune checkpoint blockade therapy has made great progress in cancer immunotherapy, but the number of patients who benefit from this therapy remains limited. In this study, we examined the effects of monotherapy with systemic low-dose resiquimod, a synthesized TLR7 agonist, and examined its combined effects with PD-L1 blockade in two PD-L1 blockade-resistant tumor models (SCCVII and Colon 26). Resiquimod monotherapy in SCCVII tumors, representing impaired CD8 + T cell function and accelerated regulatory T cells (Tregs) within the tumors, efficiently reduced tumor growth with more recruitment of CD8 + T cells and a reduction of Treg. The results of resiquimod monotherapy in Colon 26, representing impaired Treg recruitment, were inferior to that in SCCVII. Combined resiquimod treatment with PD-L1 blockade exerted clear additional effects, as it was associated with reduced tumor size, attenuation of Tregs, and an increased ratio of CD8 + T cells/Tregs in both tumors. Systemic administration of low-dose resiquimod induced a transient and rapid activation of plasmacytoid and conventional dendritic cells, resulting in enhanced priming of T cells in regional lymph nodes. Experiments with more limited doses of resiquimod that did not yield beneficial effects after single treatment, showed additional effects to PD-L1 blockade and comparable antitumor effects when the frequency of anti-PD-L1 therapy was decreased. Our results suggest that systemic administration of low-dose resiquimod is useful as a companion drug to PD-1/PD-L1 blockade therapy. Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests. |
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| فهرسة مساهمة: | Keywords: TLR7 agonist; companion drug; immune checkpoint blockade; regulatory T cells; resiquimod |
| تواريخ الأحداث: | Date Created: 20180324 Latest Revision: 20191120 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5862579 |
| DOI: | 10.18632/oncotarget.24327 |
| PMID: | 29568358 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1949-2553 |
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| DOI: | 10.18632/oncotarget.24327 |