Background: Allicin has demonstrated promoting effects on the sensitivity of non-small cell lung cancer (NSCLC) cells to radiotherapy. Herein, we further explore the mechanism by which allicin improves NSCLC immunotherapy.

Methods: NSCLC cells were subjected to different concentrations of allicin, where protein levels of lysine demethylase 5B (KDM5B) and SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) were measured. To unveil the mechanism of allicin, KDM5B overexpression plasmid and short hairpin RNA for SETDB1 (shSETDB1) were first constructed, and transfected into cells. The basic function and molecular expressions of NSCLC cells were examined. In vivo studies were performed through constructing hormonal tumour mice model. After administration of allicin and/or anti-programmed death receptor 1 (PD-1), changes in tumour growth, KDM5B and SETDB1 expressions, and immune cell infiltration were analyzed by tumour volume measurement, differentiation assays, immunohistochemical staining, and flow cytometry.

Results: Allicin down-regulated KDM5B and SETDB1 protein expressions in NSCLC cells (p < 0.05). Allicin inhibited NSCLC cell viability, migration and invasion, while promoting apoptosis (p < 0.05). Overexpression of KDM5B counteracted the therapeutic effect of allicin, while shSETDB1 reversed the effect of KDM5B (p < 0.05). In vivo, allicin significantly inhibited the growth of transplanted tumours, repressed the expressions of KDM5B and SETDB1, promoted CD8+ T-cell infiltration and reduced the proportion of tumour-associated macrophages (TAM) in the tumour (p < 0.05). With the addition of anti-PD-1 therapy, allicin showed synergistic adjuvant effects (p < 0.05).

Conclusion: Allicin inhibits the malignant function of NSCLC cells by regulating KDM5B/SETDB1 and potentiates the suppressing effect of anti-PD-1 therapy on tumour growth.