An exopolysaccharide-containing yogurt preserves CCR6 + CD4 + T Cells: Th7R, and may enhance immunotherapy responses in lung cancer patients

Background: Anti-tumor T-cell immunity is strongly influenced by the host immune state, known as the cancer-immune set point, in which gut immunity plays an essential role. Kawanabe-Matsuda et al. demonstrated in tumor-bearing mice that oral intake of purified exopolysaccharides derived from Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (R-1 EPS) induces CCR6 + T cells in Peyer's patches and enhances the antitumor efficacy of immune checkpoint inhibitors. A randomized controlled study also reported that 4-week continuous consumption of yogurt containing R-1 EPS increases CCR6 + T-cell subsets in the peripheral blood of healthy volunteers. We previously identified a novel CCR4 - CCR6 + CD4 + T-cell cluster, Th7R, enriched in advanced non-small cell lung cancer (NSCLC) patients who responded to PD-1 blockade therapy. Pre-treatment Th7R predicted ICI efficacy, and long-term survivors maintained a high proportion of Th7R after therapy. Objective: To analyze longitudinal changes in T-cell subsets in patients with histologically confirmed lung cancer who consumed yogurt fermented by L. bulgaricus OLL1073R-1 containing R-1 EPS. Methods: Peripheral blood was collected before intake, after 4 weeks of yogurt consumption, and 4 weeks after discontinuation. Changes in T-cell immune markers were evaluated using the Welch test and correlation analyses. Adverse events and the influence of concurrent cancer treatments were assessed. Results: By August 15, 2025, 91 NSCLC patients were enrolled (median age 73 years; 70 males). Participants included stage II-III patients who received neoadjuvant therapy plus surgery or chemoradiotherapy, and patients with advanced or recurrent disease receiving systemic therapy. Treatments included targeted therapy (n=5), pembrolizumab (n=15), ipilimumab plus nivolumab (n=51), cytotoxic agents plus pembrolizumab (n=2), chemoradiotherapy (n=3), and neoadjuvant cytotoxic therapy plus nivolumab (n=9). In the PD-1 inhibitor group, an increase in peripheral GZMB + CD8 + T cells was observed. Moreover, compared with historical data, the pembrolizumab-induced reduction of Th7R cells was attenuated. In the pembrolizumab subgroup with PD-L1 TPS ≥50%, treatment efficacy was favorable relative to historical controls (ORR 58.3%; DCR 91.7%). Notably, the neoadjuvant cohort achieved a 100% response rate. Conclusion: Intake of yogurt containing R-1 EPS may enhance the efficacy of immuno-oncology therapies by suppressing the decline of Th7R cells.