Fecal microbiota transplantation for advanced non-small cell lung cancer with secondary PD-1 resistance efficacy prognostic factors and microbiome diversity analysis
Abstract
Background Acquired resistance to programmed cell death protein 1 (PD-1) inhibitors represents a major therapeutic challenge in advanced non-small cell lung cancer (NSCLC). Increasing evidence suggests that gut microbiota dysbiosis contributes to immunotherapy resistance. Fecal microbiota transplantation (FMT) has emerged as a potential strategy to restore antitumor immunity, yet its role in PD-1–resistant NSCLC remains insufficiently explored. Methods This prospective, single-arm phase II study enrolled patients with stage IIIB–IV NSCLC who developed secondary resistance after prior PD-1–based therapy. Patients received oral capsule-based FMT combined with PD-1 inhibitor rechallenge and chemotherapy. Treatment efficacy was assessed using objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Gut microbiota composition was analyzed by 16 S rRNA sequencing, and immune cell subsets were evaluated by flow cytometry. Cox regression analysis was performed to identify prognostic factors. Results A total of 27 patients were enrolled, of whom 8 achieved partial response, yielding an ORR of 29.6% and a disease control rate of 63.0%. Median PFS and OS were 6.8 months (95% CI: 2.1–11.6) and 11.1 months (95% CI: 6.4–15.9), respectively. Post-FMT, responders exhibited significantly increased gut microbial diversity and distinct microbial enrichment compared with non-responders. Enhanced infiltration of CD8⁺ T-cell subsets and reduced regulatory T-cell…
Read the paper
Related studies
- Bile Acid 7α-Dehydroxylating Gut Bacteria Secrete Antibiotics that Inhibit Clostridium difficile: Role of Secondary Bile Acids
- Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome
- Altered gut microbiome composition and function are associated with gut barrier dysfunction in healthy relatives of patients with Crohn's disease
- Diet, obesity, and the gut microbiome as determinants modulating metabolic outcomes in a non-human primate model
- Immune Impairment Associated with Vitamin A Deficiency: Insights from Clinical Studies and Animal Model Research
- Glyphosate-based herbicides influence antioxidants, reproductive hormones and gut microbiome but not reproduction: A long-term experiment in an avian model
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.