Journal Article
. 2021 Aug; 174:105829.
doi: 10.1016/j.phrs.2021.105829.

Lenvatinib enhances T cell immunity and the efficacy of adoptive chimeric antigen receptor-modified T cells by decreasing myeloid-derived suppressor cells in cancer

Mengmeng Lu 1 Xiaokang Zhang 1 Xiaoge Gao 1 Shishuo Sun 1 Xiaohuan Wei 1 Xiaolei Hu 1 Chao Huang 1 Heng Xu 1 Bixi Wang 1 Wei Zhang 1 Zhen Li 1 Xinhui Feng 1 Junnian Zheng 2 Qing Zhang 3 
Affiliations
  • PMID: 34411731
  •     1 citations

Abstract

Background: Lenvatinib, a tyrosine kinase inhibitor, has been approved for the treatment of several cancers. However, its regulatory activity and related mechanisms on T cell antitumour immunity need to be further investigated.

Methods: The antitumour activity of lenvatinib in immunocompetent and immunodeficient mice was compared to determine the role of T cell immunity. The antitumour activity of T cells was analysed by cytokine production and adoptive T cell therapy. The immunosuppressive effects of MDSCs on T cells were determined by detecting cytokine production in T cells after being cocultured with MDSCs. The adjuvant immunotherapy effect of lenvatinib was determined by combination therapy with CAR-T cells targeted carbonic anhydrase IX (CAIX) in a murine renal cancer model.

Results: The antitumour activity of lenvatinib was greater in immunocompetent mice than in immunodeficient mice and was attenuated by CD8+T cell depletion. Lenvatinib increased proliferation, tumour infiltration and antitumour activity of T cells. Importantly, adoptive transfer of lenvatinib-treated T cells showed a long-term antitumour response in vivo. Mechanistically, lenvatinib upregulated T cell-related chemokines (CXCL10 and CCL8) in tumours and decreased the frequency and immunosuppressive activity of MDSCs. Furthermore, lenvatinib enhanced the efficacy of CAR-T cells in a murine renal cancer model.

Conclusion: Our study revealed novel antitumour mechanisms of lenvatinib by enhancing T cell-mediated antitumour immunity. These findings are of great significance for guiding the clinical use of lenvatinib and provide a good candidate for future combination therapy with T-cell therapies or other immunotherapies.

Keywords: CAR-T; CCL8; CXCL10; Carbonic anhydrase IX; Lenvatinib; MDSC.

Lenvatinib Plus Camrelizumab vs. Lenvatinib Monotherapy as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Cohort Study.
Qi Li, Mengran Cao, +9 authors, Jinzhang Chen.
Front Oncol, 2022 Mar 15; 12. PMID: 35280760    Free PMC article.