Combination of 3-(Trihydroxygermyl)propanoic Acid (THGP) and Lipopolysaccharide Promotes Macrophage Differentiation to M1, and Antitumor Activity.

Background/aim: Macrophage polarization plays a critical role in cancer immunotherapy. This study aimed to evaluate the synergistic effects of 3-(trihydroxygermyl)propanoic acid (THGP), an organogermanium compound, and the immunostimulant lipopolysaccharide (LPS) derived from Pantoea agglomerans on M1 macrophage differentiation and antitumor activity.

Materials and methods: RAW 264.7 cells were treated with THGP, LPS, or their combination for 1, 4, or 10 days. Morphological changes, M1 marker (CD80 and CD86) expression, cytokine production (IL-1β and IL-6), phagocytic activity, and cytotoxicity against B16-F10 melanoma cells were assessed using microscopy, qPCR, western blotting, immunofluorescence staining, and luciferase assays.

Results: After one day of treatment, LPS treatment, both alone or in combination with THGP, increased M1 marker expression. By day 4, both agents individually induced M1 differentiation; their combination had a synergistic effect on cytokine production and phagocytic activity. Antitumor effects were observed only with the combined treatment. After 10 days, single and combined treatments resulted in comparable phagocytic and antitumor activities.

Conclusion: The combination of THGP and LPS synergistically promotes M1 macrophage differentiation and enhances phagocytic and antitumor activities through distinct mechanisms. These findings suggest potential applications of this combination in cancer immunotherapy.