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

Melanoma remains a therapeutic challenge due to its aggressive nature and limited efficacy of conventional treatments. This study investigates the antimelanoma potential of Lactiplantibacillus plantarum FLPL05, a probiotic strain derived from Chinese longevity individual, using a B16F10 melanoma-bearing murine model and macrophage-tumor cell coculture system. The strain administration dose-dependently inhibited tumor growth by 55.7-77.7%, restored thymic/splenic indexes, and reversed tumor-induced lymphocyte exhaustion, elevating splenocyte proliferation under the stimulation of ConA and LPS with a rate of 147.3% and 179.5%, respectively. Mechanistically, the strain upregulated Th1 cytokines (TNF-α, IFN-γ, IL-2) in tumor tissues, polarized macrophages toward a tumoricidal M1 phenotype, and activated intrinsic/extrinsic apoptotic pathways (Bax/Bcl-2 ratio to a 5.3-fold; Caspase-8 to 2.9-fold Caspase-9 to 1.6-fold). Concurrently, it suppressed epithelial-mesenchymal transition (down-regulating the transcription of N-cadherin, Snail, and Twist, up-regulating E-cadherin) and angiogenesis (down-regulating the transcription of VEGF, FGF2, and MMP-9, by 66%, 22%, and 37%, respectively). Coculture experiments revealed 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). Notably, the strain synergized with 5-fluorouracil (5-FU), enhancing efficacy while mitigating chemotherapy-induced splenomegaly. These findings demonstrate that L. plantarum FLPL05 may function as both a dietary supplement and a promising natural adjuvant, capable of enhancing the efficacy of conventional therapies for melanoma treatment.