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...
Guardado en:
| Autores principales: | , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Wiley
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/5cc69c6a6dee4d3aa9ceef8a294a2281 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:5cc69c6a6dee4d3aa9ceef8a294a2281 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:5cc69c6a6dee4d3aa9ceef8a294a22812021-11-22T09:08:47ZThe immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma2045-763410.1002/cam4.4312https://doaj.org/article/5cc69c6a6dee4d3aa9ceef8a294a22812021-11-01T00:00:00Zhttps://doi.org/10.1002/cam4.4312https://doaj.org/toc/2045-7634Abstract 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.Jie ZhuPeiqi FangChong WangMeixiu GuBaishen PanWei GuoXinrong YangBeili WangWileyarticleCTL/Treg ratioHCCimmunomodulatory activitylenvatinibNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Medicine, Vol 10, Iss 22, Pp 7977-7987 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
CTL/Treg ratio HCC immunomodulatory activity lenvatinib Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
CTL/Treg ratio HCC immunomodulatory activity lenvatinib Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma |
| publisher |
Wiley |
| publishDate |
2021 |
| url |
https://doaj.org/article/5cc69c6a6dee4d3aa9ceef8a294a2281 |
| work_keys_str_mv |
AT jiezhu theimmunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT peiqifang theimmunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT chongwang theimmunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT meixiugu theimmunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT baishenpan theimmunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT weiguo theimmunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT xinrongyang theimmunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT beiliwang theimmunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT jiezhu immunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT peiqifang immunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT chongwang immunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT meixiugu immunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT baishenpan immunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT weiguo immunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT xinrongyang immunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma AT beiliwang immunomodulatoryactivityoflenvatinibpromptsthesurvivalofpatientswithadvancedhepatocellularcarcinoma |
| _version_ |
1718417797037424640 |