Abstract 6527: Ginseng polysaccharides circumvent acquired resistance to anti-pd1 immunotherapy in patients with non-small cell lung cancer

In 2021, we demonstrated that ginseng polysaccharides (GPs) enhance the therapeutic efficacy of anti-programmed cell death 1 (PD-1) immunotherapy by modulating the gut microbiota. GPs may serve as a beneficial dietary supplement for non-small cell lung cancer (NSCLC) patients undergoing immunotherapy. We reported GPs increased the anti-tumor response to αPD-1 mAb by increasing the microbial metabolites valeric acid, and decreasing the ratio of Kyn/Trp, which contributed to the suppression of Treg and induction of Teff cells. Besides, the microbial analysis of patients fecal samples indicated that the abundance of Parabacteroides distasonis and Bacteroides vulgatus was higher in responders to anti-PD-1 blockade than non-responders. In this study, we aim to further validate and extend these previous findings. Therefore, we designed the first World Health Organization-registered clinical trial of traditional Chinese medicine combined with immunotherapy (ChiCTR2100046431) to investigate whether oral administration of GPs can circumvent acquired resistance to anti-PD-1 immunotherapy in patients with advanced NSCLC. Eligible acquired drug-resistant patients continued the use of PD-1 inhibitors as per their initial immunotherapy regimen and initiated oral administration of GPs twice daily upon enrolling in the trial. Longitudinal stool and blood samples were systematically collected from participants. The gut microbiome was profiled through third-generation amplicon sequencing. Simultaneously, comprehensive analyses of blood samples were conducted, utilizing metabolomics and quantification of cytokines. Clinical trial results showed that five patients regained response to anti-PD-1 immunotherapy, with an objective response rate of 50%. Comprehensive analysis of the gut microbiome and blood samples revealed a significant increase in the relative abundance of Parabacteroides distasonis after treatment, along with a significant upregulation of tumor necrosis factor-α (TNF-α) and various metabolites levels in the blood. In this study, we report the first case series of patients with advanced NSCLC with acquired resistance to anti-PD-1 immunotherapy who were treated with oral administration of GPs, which resulted in overcoming acquired resistance and regaining a response to immune checkpoint inhibitors. These preliminary data provide valuable clinical clues for overcoming the acquired resistance to PD-1 immunotherapy. Citation Format: Jumin Huang, Ziming Wang, Yabing Cao, Wenhua Liang, Elaine Lai-Han Leung. Ginseng polysaccharides circumvent acquired resistance to anti-pd1 immunotherapy in patients with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6527.