Synergistic Anti-Tumor and Immunomodulatory Effects of Sporoderm-Removed Ganoderma Lucidum Spore Powder and Anti-PD-L1 Antibody in Lung Cancer Mice

Abstract Background The therapeutic efficacy of PD-1/PD-L1 inhibitors in lung cancer management remains suboptimal. Sporoderm-removed Ganoderma Lucidum Spore Powder (RGLS), an immunostimulant, has been shown to amplify the anti-tumor effects of anti-PD-L1 antibodies (αPD-L1). However, the detailed molecular underpinnings of this enhancement are not yet fully elucidated. This study aimed to elucidate the antitumor mechanism and immunomodulatory effect of RGLS in synergistic relationship with αPD-L1 in lung cancer. Methods Employing network pharmacology approaches, this research analyzed the multifaceted target pathways of RGLS in lung cancer. High-Performance Liquid Chromatography (HPLC) facilitated the identification of RGLS constituents. In the established Lewis lung cancer tumor-bearing mouse model, the effects of RGLS, αPD-L1, and their combination were investigated, focusing on tumor growth, T cell responses, and the dynamics of myeloid-derived suppressor cells (MDSCs) within tumor microenvironments. Results Our network analysis revealed 26 bioactive components of RGLS and identified 227 potential lung cancer targets, among which PD-L1 had a significant response effect with 20 core targets. HPLC identified 14 triterpenoid components. Notably, the combination of RGLS and αPD-L1 significantly inhibited tumor growth, optimized the CD4⁺/CD8⁺ T cell ratio in tumor tissue, increased IL-2 and IFN-γ levels, enhanced cytotoxic T lymphocyte (CTL) activity, and inhibited MDSC recruitment. Conclusion The synergistic application of RGLS and αPD-L1 in lung cancer treatment significantly improves immune responsiveness and reduces tumor-associated MDSCs, surpassing the efficacy of sole αPD-L1 application. This study underscores RGLS's burgeoning potential in bolstering lung cancer immunotherapy, paving the way for its clinical applications.