Additive anti-tumor and immunomodulatory effects of Sporoderm-removed Ganoderma lucidum spore powder and anti-PD-L1 antibody in lung cancer mice.

Qiong Wang, Xiaorong Zheng, Zengyu Zhang, Min Hao, Jianwei Jiang, Junfei Li, Hongyan Zhang

Discov Oncol

Mar 21, 2026

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Abstract

BACKGROUND: The therapeutic efficacy of programmed cell death-1 (PD-1)/programmed cell death ligand-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 additive effect relationship withαPD-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 andαPD-L1 significantly inhibited tumor growth, optimized the CD4+/CD8+ T cell ratio in tumor tissue, increased IL-2 and IFN-γlevels, enhanced cytotoxic T lymphocyte (CTL) activity, and inhibited MDSCs recruitment. CONCLUSION: The additive effect application of RGLS andαPD-L1 in lung cancer treatment significantly improves immune responsiveness and reduces tumor-associated MDSCs, surpassing the efficacy of soleαPD-L1 application. This study underscores RGLS’s burgeoning potential in bolstering lung cancer immunotherapy, paving the way for its clinical applications.