The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma
Abstract Background Lenvatinib is a novel multiple receptor tyrosine kinase inhibitor used for hepatocellular carcinoma (HCC) treatment. Although its main function is to suppress VEGFR and FGFR pathway, its immunomodulatory activity in HCC is not elucidated. Thus, this study aimed to investigate the...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-11-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.4312 |
| _version_ | 1818844209327636480 |
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| author | Jie Zhu Peiqi Fang Chong Wang Meixiu Gu Baishen Pan Wei Guo Xinrong Yang Beili Wang |
| author_facet | Jie Zhu Peiqi Fang Chong Wang Meixiu Gu Baishen Pan Wei Guo Xinrong Yang Beili Wang |
| author_sort | Jie Zhu |
| collection | DOAJ |
| description | Abstract Background Lenvatinib is a novel multiple receptor tyrosine kinase inhibitor used for hepatocellular carcinoma (HCC) treatment. Although its main function is to suppress VEGFR and FGFR pathway, its immunomodulatory activity in HCC is not elucidated. Thus, this study aimed to investigate the immunomodulatory capability of lenvatinib in HCC. Material and methods Totally 47 patients with HCC were enrolled in this study, and the immune cells and serum cytokine profiles before initiation of treatment and after 1 and 3 months were measured. The immune checkpoint receptors on the immune cells were also evaluated. Kaplan–Meier survival estimate and log rank tests were used to assess the prognostic value. Result The frequency of T helper (Th) cells and T regulatory (Treg) cells reduced after lenvatinib treatment, while cytotoxic T lymphocyte (CTL) cells increased significantly. The cytokine profiles showed IL‐2, IL‐5, IFN‐γ increased; other cytokines including IL‐6, IL‐10, TNF‐ α and TNF‐ β decreased with lenvatinib therapy. Furthermore, the PD‐1 and TIM‐3 expressed on CTL had greatly decreased; the expression of TIM‐3 and CTLA‐4 was reduced on Treg cells as well. Besides, the new index CTL/Treg ratio was created, and low ratio was associated with the unfavorable outcome of HCC patients. Conclusion Our results confirmed that lenvatinib is capable of improving patients’ immune status, saving the effector cells from exhaustion status and inhibiting the number and function of immunosuppressive cells. The novel index CTL/Treg ratio qualifies as a predictor for the outcome of patients with lenvatinib therapy. |
| first_indexed | 2024-12-19T05:10:07Z |
| format | Article |
| id | doaj.art-5cc69c6a6dee4d3aa9ceef8a294a2281 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-19T05:10:07Z |
| publishDate | 2021-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-5cc69c6a6dee4d3aa9ceef8a294a22812022-12-21T20:34:49ZengWileyCancer Medicine2045-76342021-11-0110227977798710.1002/cam4.4312The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinomaJie Zhu0Peiqi Fang1Chong Wang2Meixiu Gu3Baishen Pan4Wei Guo5Xinrong Yang6Beili Wang7Department of Laboratory Medicine, Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Laboratory Medicine, Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Laboratory Medicine, Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Laboratory Medicine, Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Laboratory Medicine, Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Laboratory Medicine, Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery, Liver Cancer Institute, Zhong Hospital Fudan University Shanghai ChinaDepartment of Laboratory Medicine, Zhongshan Hospital Fudan University Shanghai ChinaAbstract Background Lenvatinib is a novel multiple receptor tyrosine kinase inhibitor used for hepatocellular carcinoma (HCC) treatment. Although its main function is to suppress VEGFR and FGFR pathway, its immunomodulatory activity in HCC is not elucidated. Thus, this study aimed to investigate the immunomodulatory capability of lenvatinib in HCC. Material and methods Totally 47 patients with HCC were enrolled in this study, and the immune cells and serum cytokine profiles before initiation of treatment and after 1 and 3 months were measured. The immune checkpoint receptors on the immune cells were also evaluated. Kaplan–Meier survival estimate and log rank tests were used to assess the prognostic value. Result The frequency of T helper (Th) cells and T regulatory (Treg) cells reduced after lenvatinib treatment, while cytotoxic T lymphocyte (CTL) cells increased significantly. The cytokine profiles showed IL‐2, IL‐5, IFN‐γ increased; other cytokines including IL‐6, IL‐10, TNF‐ α and TNF‐ β decreased with lenvatinib therapy. Furthermore, the PD‐1 and TIM‐3 expressed on CTL had greatly decreased; the expression of TIM‐3 and CTLA‐4 was reduced on Treg cells as well. Besides, the new index CTL/Treg ratio was created, and low ratio was associated with the unfavorable outcome of HCC patients. Conclusion Our results confirmed that lenvatinib is capable of improving patients’ immune status, saving the effector cells from exhaustion status and inhibiting the number and function of immunosuppressive cells. The novel index CTL/Treg ratio qualifies as a predictor for the outcome of patients with lenvatinib therapy.https://doi.org/10.1002/cam4.4312CTL/Treg ratioHCCimmunomodulatory activitylenvatinib |
| spellingShingle | Jie Zhu Peiqi Fang Chong Wang Meixiu Gu Baishen Pan Wei Guo Xinrong Yang Beili Wang The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma Cancer Medicine CTL/Treg ratio HCC immunomodulatory activity lenvatinib |
| title | The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma |
| title_full | The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma |
| title_fullStr | The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma |
| title_full_unstemmed | The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma |
| title_short | The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma |
| title_sort | immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma |
| topic | CTL/Treg ratio HCC immunomodulatory activity lenvatinib |
| url | https://doi.org/10.1002/cam4.4312 |
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