A probiotic from longevity populations: Lactiplantibacillus plantarum FLPL05 as a functional food adjuvant for melanoma via immunomodulation and tumor suppression.

L. plantarum FLPL05 dose-dependently inhibited tumor growth in a B16F10 melanoma-bearing murine model.

• Tumor inhibition ranged from 55.7% to 77.7% depending on the dose administered.
• The strain was derived from a Chinese longevity individual.
• A B16F10 melanoma-bearing murine model was used as the primary in vivo system.

FLPL05 restored immune organ indexes and reversed tumor-induced lymphocyte exhaustion.

• The strain restored thymic and splenic indexes that had been suppressed by tumor growth.
• Splenocyte proliferation under ConA stimulation was elevated to 147.3%.
• Splenocyte proliferation under LPS stimulation was elevated to 179.5%.

FLPL05 upregulated Th1 cytokines and polarized macrophages toward a tumoricidal M1 phenotype.

• Th1 cytokines upregulated in tumor tissues included TNF-α, IFN-γ, and IL-2.
• Macrophage polarization was directed toward the M1 phenotype, which is associated with tumoricidal activity.
• Coculture experiments confirmed macrophage-mediated tumor apoptosis and metastasis inhibition via FLPL05-induced NO and cytokine secretion (TNF-α, IFN-γ, IL-2, IL-6, and IL-1β).

FLPL05 activated both intrinsic and extrinsic apoptotic pathways in tumor cells.

• The Bax/Bcl-2 ratio was elevated to 5.3-fold.
• Caspase-8 expression was increased to 2.9-fold, indicating activation of the extrinsic apoptotic pathway.
• Caspase-9 expression was increased to 1.6-fold, indicating activation of the intrinsic apoptotic pathway.

FLPL05 suppressed epithelial-mesenchymal transition (EMT) in melanoma.

• Transcription of EMT-promoting genes N-cadherin, Snail, and Twist was downregulated.
• Transcription of the epithelial marker E-cadherin was upregulated.
• These findings were based on transcriptional-level measurements in the tumor model.

FLPL05 suppressed tumor angiogenesis by downregulating key angiogenic factors.

• VEGF transcription was downregulated by 66%.
• FGF2 transcription was downregulated by 22%.
• MMP-9 transcription was downregulated by 37%.

FLPL05 synergized with 5-fluorouracil (5-FU) and mitigated chemotherapy-induced side effects.

• The combination of FLPL05 and 5-FU enhanced antimelanoma efficacy compared to either treatment alone.
• FLPL05 administration mitigated 5-FU-induced splenomegaly.
• This finding suggests potential utility of FLPL05 as an adjuvant to conventional chemotherapy.

A macrophage-tumor cell coculture system was used to mechanistically investigate FLPL05's indirect antitumor effects.

• The coculture system revealed that FLPL05-conditioned macrophages mediated tumor cell apoptosis.
• Macrophage-derived NO production was identified as a mechanism of tumor suppression.
• Cytokines secreted by FLPL05-stimulated macrophages included TNF-α, IFN-γ, IL-2, IL-6, and IL-1β.