{
  "abstract": "Background Immune checkpoint inhibitors (ICIs), such as anti-PD-1 antibodies, have revolutionized cancer treatment, but their efficacy remains limited in many patients, including those with non-small cell lung cancer (NSCLC). 1 Recent studies suggest that gut microbiota play a crucial role in modulating host response to ICIs.2 Bojungikki-Tang (BJIKT) is a clinically used herbal formula known for its immunoregulatory properties, with evidence from both clinical studies showing benefits in restoring immune function and improving cancer-related symptoms, and preclinical studies demonstrating anticancer and immunomodulatory effects.3 In this study, we examined the associated changes in gut microbiota, systemic metabolism, and immune cell profiles and evaluated the combined antitumor effects of BJIKT and anti-PD-1 therapy.Methods DBA/2 mice bearing subcutaneous KLN205 murine NSCLC tumors were treated with anti-PD-1 antibodies in combination with orally administered BJIKT. Tumor progression was monitored, and immune responses were assessed through flow cytometry of splenic and tumor-infiltrating lymphocytes, focusing on CD8 + cytotoxic T cells, CD4+ helper T cells, and regulatory T cells (Tregs). Plasma cytokine concentrations were measured, and metabolomic profiling was conducted. Shotgun metagenomic sequencing was performed to analyze gut microbial composition.Results Flow cytometry revealed that BJIKT treatment led to increased infiltration of CD8 + and CD4+ T cells and a reduction in Treg cells in both spleen and tumor tissues. Plasma cytokine analysis showed that BJIKT elevated pro-inflammatory cytokines. Metabolomic shifts were also observed in response to BJIKT, indicating metabolic reprogramming. Furthermore, microbiome analysis revealed an increased abundance of Lactobacillus and Rikenellaceae, alongside decreased levels of Bacteroides and Desulfovibrionaceae, suggesting that BJIKT created a favorable microbial environment for antitumor immunity. Combination therapy with BJIKT and anti-PD-1 significantly suppressed tumor growth compared to monotherapy.Conclusions BJIKT enhances the therapeutic efficacy of anti-PD-1 immune checkpoint blockade by modulating gut microbiota composition, improving systemic immune responses, and altering host metabolism. These findings support the integration of herbal therapeutics like BJIKT as adjuvants in cancer immunotherapy strategies.References Shiravand Y, Khodadadi F, Kashani SMA, et al. Immune checkpoint inhibitors in cancer therapy. Curr Oncol. 2022;29(5):3044–3060.Zheng Y, Wang T, Tu X, et al. Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma. J Immunother Cancer. 2019;7(1):193.Cho E, Na SW, Jeong MK. Therapeutic and immunomodulatory effects of Bojungikki-tang on cancer: a scoping review. BMC Cancer. 2024;24(1):1169.Ethics Approval The experimental protocols were approved by the Animal Care and Use Committee of the Korea Institute of Oriental Medicine (Approval No. 22-111).",
  "authors": [
    {
      "affiliations": [
        "Korea Institute of Oriental Medicine, Daejeon, Republic of Korea"
      ],
      "name": "Se Won Na"
    },
    {
      "affiliations": [
        "Korea Institute of Oriental Medicine, Daejeon, Republic of Korea"
      ],
      "name": "Mibae Jeong"
    },
    {
      "affiliations": [
        "Korea Institute of Oriental Medicine, Daejeon, Republic of Korea"
      ],
      "name": "Jin-Mu Yi"
    },
    {
      "affiliations": [
        "Korea Institute of Oriental Medicine, Daejeon, Republic of Korea"
      ],
      "name": "Jaemoo Chun"
    },
    {
      "affiliations": [
        "Korea Institute of Oriental Medicine, Daejeon, Republic of Korea"
      ],
      "name": "Mi-Kyung Jeong"
    }
  ],
  "title": "1135 Bojungikki-tang enhances anti-PD-1 immunotherapy in NSCLC by modulating gut microbiota and immune responses",
  "uid": "0c8f2436-c6f1-5252-ba5b-220e7a7dacfd"
}