Intratumoral Delivery of Probiotic Ligilactobacillus salivarius H22A013 Modulates the Melanoma Microenvironment and Enhances Trametinib Efficacy

Melanoma urgently needs better treatments. While probiotics show promise indirectly via the gut-tumor axis, challenges like variability and safety exist. This study introduces a novel strategy: intratumoral injection of the native probiotic Ligilactobacillus salivarius H22A013 (L. salivarius H22A013) to target the tumor microenvironment (TME). Combined with trametinib, this approach significantly upregulated IFN-gamma and TNF-alpha, increased immune cell infiltration into tumors, and enhanced cellular immunity. Remarkably, L. salivarius H22A013 migrated to the gut, altering gut microbiota structure and metabolism. This led to reduced spermine/spermidine degradation and increased valine synthesis, further modulating immunity and suppressing tumor growth. Crucially, this strategy bypasses traditional indirect gut-axis modulation and avoids the safety concerns of engineered probiotics, offering a novel application for native probiotics in cancer therapy.