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Cancer Cell Int. 2019 Mar 21;19:68. doi: 10.1186/s12935-019-0789-y. eCollection 2019.

Lycopene improves the efficiency of anti-PD-1 therapy via activating IFN signaling of lung cancer cells.

Author information

1
Department of Respiratory Medicine, The Fifth People's Hospital of Wuxi City, Wuxi, 214016 China.

Abstract

Background:

Monoclonal antibodies targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) have been developed to treat cancers including lung cancer. In this study, we aimed to investigate whether lycopene could promote the effect of anti-PD-1 treatment on lung cancer.

Methods:

Tumor formation assay was conducted. Immune reactions were assessed by detecting several cytokine levels using enzyme-like immunosorbent assay. T cell activity was analyzed using cytometry. The mechanism of lycopene action was investigated using Western blot, quantitative real-time polymerase chain reaction and bisulfite sequencing analysis.

Results:

After the mice injected with Lewis lung carcinoma (LLC) cells were sacrificed, we found that combined lycopene and anti-PD-1 reduced the tumor volume and weight compared to control treatment. Cell apoptosis in the tumor tissues was significantly enhanced in mice with combined lycopene and anti-PD-1 treatment in comparison with those of either lycopene or anti-PD-1 alone. Furthermore, lycopene could assist anti-PD-1 to elevate the levels of interleukin (IL)-1 and interferon (IFN) γ while reduce the levels of IL-4 and IL-10 in the spleen of mice injected with LLC cells. Lycopene treatment increased the CD4+/CD8+ ratio in the spleen and promoted IFNγ-expressing CD8+ T cells in tumor tissues. Upon IFNγ stimulation, lycopene diminished PD-L1 expression via activating JAK and repressing phosphorylation of AKT.

Conclusion:

Our results have demonstrated that lycopene could be used as a potential adjuvant drug to synergistically improve the efficiency of anti-PD-1 therapy.

KEYWORDS:

Interferon (IFN) γ; Interferon-regulatory factor (IRF) proteins; Lung cancer; Lycopene; Programmed death-1 receptor (PD-1)

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