Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy
Anlotinib is a new multitarget tyrosine kinase inhibitor for tumor angiogenesis, and its monotherapy exhibits a decent clinical efficacy. However, the process of combining Anlotinib and immune checkpoint therapy to achieve optimal antitumor effects while limiting side effects remains unclear. In thi...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.937924/full |
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| author | Peng Fan Peng Fan Huiping Qiang Zhenhua Liu Qi Zhao Ying Wang Tingkun Liu Xuan Wang Tianqing Chu Yuhui Huang Wei Xu Songbing Qin |
| author_facet | Peng Fan Peng Fan Huiping Qiang Zhenhua Liu Qi Zhao Ying Wang Tingkun Liu Xuan Wang Tianqing Chu Yuhui Huang Wei Xu Songbing Qin |
| author_sort | Peng Fan |
| collection | DOAJ |
| description | Anlotinib is a new multitarget tyrosine kinase inhibitor for tumor angiogenesis, and its monotherapy exhibits a decent clinical efficacy. However, the process of combining Anlotinib and immune checkpoint therapy to achieve optimal antitumor effects while limiting side effects remains unclear. In this study, we found that effective low-dose Anlotinib was sufficient to inhibit tumor growth while reducing side effects compared with high doses. Effective low-dose Anlotinib treatments induced durable tumor vascular normalization and improved anti-PD-1 therapy in both short- and long-term treatment regimens. Mechanistically, the combination therapy increased the proportions of intratumoral CD4+ T, CD8+ T, and NK cells. Anlotinib-associated antitumor effects were independent of interferon γ; however, the combination therapy required CD8+ T cells to suppress tumor growth. Together, these results suggest that the combination of effective low-dose Anlotinib and PD-1 blockade induces durable antitumor effects with fewer side effects. Our findings indicate that antiangiogenic treatments combined with immune checkpoint therapy at an effective low-dose, rather than a tolerable high dose, would be more efficacious and safer. |
| first_indexed | 2024-04-14T06:01:48Z |
| format | Article |
| id | doaj.art-8e9116e1a93b461385ff5878c1d0b1ee |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T06:01:48Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8e9116e1a93b461385ff5878c1d0b1ee2022-12-22T02:08:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.937924937924Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapyPeng Fan0Peng Fan1Huiping Qiang2Zhenhua Liu3Qi Zhao4Ying Wang5Tingkun Liu6Xuan Wang7Tianqing Chu8Yuhui Huang9Wei Xu10Songbing Qin11Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, ChinaDepartment of Experimental Medicine, University of Rome “Tor Vergata”, Rome, ItalyDepartment of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, ChinaDepartment of Immunology, Innovent Biologics, Inc., Suzhou, ChinaDepartment of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, ChinaDepartment of Immunology, Innovent Biologics, Inc., Suzhou, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaAnlotinib is a new multitarget tyrosine kinase inhibitor for tumor angiogenesis, and its monotherapy exhibits a decent clinical efficacy. However, the process of combining Anlotinib and immune checkpoint therapy to achieve optimal antitumor effects while limiting side effects remains unclear. In this study, we found that effective low-dose Anlotinib was sufficient to inhibit tumor growth while reducing side effects compared with high doses. Effective low-dose Anlotinib treatments induced durable tumor vascular normalization and improved anti-PD-1 therapy in both short- and long-term treatment regimens. Mechanistically, the combination therapy increased the proportions of intratumoral CD4+ T, CD8+ T, and NK cells. Anlotinib-associated antitumor effects were independent of interferon γ; however, the combination therapy required CD8+ T cells to suppress tumor growth. Together, these results suggest that the combination of effective low-dose Anlotinib and PD-1 blockade induces durable antitumor effects with fewer side effects. Our findings indicate that antiangiogenic treatments combined with immune checkpoint therapy at an effective low-dose, rather than a tolerable high dose, would be more efficacious and safer.https://www.frontiersin.org/articles/10.3389/fimmu.2022.937924/fullEffective low-doseAnlotinibAnti-PD1 therapyCD8+ T cellLong-term vascular normalization |
| spellingShingle | Peng Fan Peng Fan Huiping Qiang Zhenhua Liu Qi Zhao Ying Wang Tingkun Liu Xuan Wang Tianqing Chu Yuhui Huang Wei Xu Songbing Qin Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy Frontiers in Immunology Effective low-dose Anlotinib Anti-PD1 therapy CD8+ T cell Long-term vascular normalization |
| title | Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy |
| title_full | Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy |
| title_fullStr | Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy |
| title_full_unstemmed | Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy |
| title_short | Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy |
| title_sort | effective low dose anlotinib induces long term tumor vascular normalization and improves anti pd 1 therapy |
| topic | Effective low-dose Anlotinib Anti-PD1 therapy CD8+ T cell Long-term vascular normalization |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.937924/full |
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