Combination Treatment of Topical Imiquimod Plus Anti-PD-1 Antibody Exerts Significantly Potent Antitumor Effect
| العنوان: | Combination Treatment of Topical Imiquimod Plus Anti-PD-1 Antibody Exerts Significantly Potent Antitumor Effect |
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| المؤلفون: | Ryota Tanaka, Manabu Fujimoto, Zhu Zhenjie, Yasuhiro Fujisawa, Kazumasa Oya, Noriko Kubota, Naoko Okiyama, Rei Watanabe, Akimasa Saito, Yuki Ichimura, Yosuke Ishitsuka, Yoshiyuki Nakamura, Hideaki Tahara |
| المصدر: | Cancers; Volume 13; Issue 16; Pages: 3948 Cancers Cancers, Vol 13, Iss 3948, p 3948 (2021) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, anti-PD-1 antibody, Combination therapy, Imiquimod, Article, combination therapy, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, imiquimod, melanoma, medicine, RC254-282, biology, business.industry, Melanoma, Wild type, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Lymph, Antibody, business, CD8, medicine.drug |
| الوصف: | Simple Summary Imiquimod (IMQ), a synthetic ligand of Toll-like receptor 7, is known to exert antitumor effects. However, the exact mechanisms of the IMQ-induced antitumor effect have not been fully understood. Although both topical IMQ treatment and anti-PD-1 antibody may be used for primary skin lesions or skin metastases of various cancers, the efficacy of each monotherapy for these lesions is insufficient. In our study using a murine tumor model, we show that IFN-γ produced by CD8+ T cells may play a crucial role in the IMQ-induced antitumor effect. In addition, IMQ upregulated PD-1 expression in T cells as well as PD-L1/PD-L2 expression in myeloid cells. Furthermore, we also found that combination therapy of topical IMQ with anti-PD-1 antibody exerted a significantly potent antitumor effect when compared with each single therapy. Therefore, the combination therapy of topical IMQ plus anti-PD-1 antibody is promising therapy for skin cancer. Abstract The exact mechanisms of the imiquimod (IMQ)-induced antitumor effect have not been fully understood. Although both topical IMQ treatment and anti-PD-1 antibody may be used for primary skin lesions or skin metastases of various cancers, the efficacy of each monotherapy for these lesions is insufficient. Using a murine tumor model and human samples, we aimed to elucidate the detailed mechanisms of the IMQ-induced antitumor effect and analyzed the antitumor effect of combination therapy of topical IMQ plus anti-PD-1 antibody. Topical IMQ significantly suppressed the tumor growth of MC38 in wildtype mice. IMQ upregulated interferon γ (IFN-γ) expression in CD8+ T cells in both the lymph nodes and the tumor, and the antitumor effect was abolished in both Rag1-deficient mice and IFN-γ-deficient mice, indicating that IFN-γ produced by CD8+ T cells play a crucial role in the IMQ-induced antitumor effect. IMQ also upregulated PD-1 expression in T cells as well as PD-L1/PD-L2 expression in myeloid cells, suggesting that IMQ induces not only T-cell activation but also T-cell exhaustion by enhanced PD-1 inhibitory signaling. Combination therapy of topical IMQ plus anti-PD-1 antibody exerted a significantly potent antitumor effect when compared with each single therapy, indicating that the combination therapy is a promising therapy for the skin lesions of various cancers. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2072-6694 |
| DOI: | 10.3390/cancers13163948 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3d8344952f1ddc6f7f9bbac61f2f236Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f3d8344952f1ddc6f7f9bbac61f2f236 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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| DOI: | 10.3390/cancers13163948 |