We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Sulforaphane enhances the antitumor response of chimeric antigen receptor T cells by regulating PD-1/PD-L1 pathway.
- Authors
Shen, Chunyi; Zhang, Zhen; Tian, Yonggui; Li, Feng; Zhou, Lingxiao; Jiang, Wenyi; Yang, Li; Zhang, Bin; Wang, Liping; Zhang, Yi
- Abstract
<bold>Background: </bold>Chimeric antigen receptor T (CAR-T) cell therapy has limited effects in the treatment of solid tumors. Sulforaphane (SFN) is known to play an important role in inhibiting tumor growth, but its effect on CAR-T cells remains unclear. The goal of the current study was to determine whether combined CAR-T cells and SFN could provide antitumor efficacy against solid tumors.<bold>Methods: </bold>The effect of combined SFN and CAR-T cells was determined in vitro using a co-culture system and in vivo using a xenograft mouse model. We further validated the effects of combination therapy in patients with cancer.<bold>Results: </bold>In vitro, the combination of SFN and CAR-T cells resulted in enhanced cytotoxicity and increased lysis of tumor cells. We found that SFN suppressed programmed cell death 1 (PD-1) expression in CAR-T cells and potentiated antitumor functions in vitro and in vivo. As a ligand of PD-1, programmed cell death ligand 1 (PD-L1) expression was also decreased in tumor cells after SFN treatment. In addition, β-TrCP was increased by SFN, resulting in higher activation of ubiquitination-mediated proteolysis of PD-L1, which induced PD-L1 degradation. The combination of SFN and CAR-T cell therapy acted synergistically to promote better immune responses in vivo compared with monotherapy. In clinical treatments, PD-1 expression was lower, and proinflammatory cytokine levels were higher in patients with various cancers who received CAR-T cells and took SFN orally than that in the control group.<bold>Conclusion: </bold>SFN improves the cytotoxicity of CAR-T cells by modulating the PD-1/PD-L1 pathway, which may provide a promising strategy for the combination of SFN with CAR-T cells for cancer immunotherapy.
- Subjects
CHIMERIC antigen receptors; PROGRAMMED death-ligand 1; PROGRAMMED cell death 1 receptors; SULFORAPHANE; TREATMENT effectiveness
- Publication
BMC Medicine, 2021, Vol 19, Issue 1, p1
- ISSN
1741-7015
- Publication type
journal article
- DOI
10.1186/s12916-021-02161-8