Immune System Modulation with Oral Vancomycin in combination with Stereotactic Body Radiotherapy (SBRT) for medically inoperable Early-Stage Non-small Cell Lung Cancer

We report the results of a randomized, open-label pilot study evaluating oral vancomycin combined with SBRT in early-stage non-small cell lung cancer. Building on prior research, vancomycin was found to enhance antitumor effects by modulating gut microbiota and boosting immune responses notably improving progression-free and overall survival (P.F.S. and O.S.). Patients treated with vancomycin (125 mg QID for 5 weeks starting one week before SBRT) showed increased expression of antigen presenation machinary in PBMCs and councurrent T-cell activation, and significant changes in gut microbiome composition and metabolite profiles, including reduced Short Chain Fatty Acids and elevated TNF-beta levels. With minimal adverse events, vancomycin appears to synergistically enhance RT-induced antitumor immunity, positioning it as a viable strategy for improving oncological outcomes. Further studies with larger cohorts are needed to confirm these results. To gain a better understanding of the effects of Vancomycin on the systemic immune response, we performed bulk RNA sequencing on PBMCs from NSCLC patients treated with either radiation therapy (RT) alone or in combination with Vancomycin (RT + Vancomycin). Bulk RNA sequencing was conducted on 17 PBMC samples, with 8 receiving only radiation therapy (RT) and 9 treated with a combination of radiation therapy and Vancomycin (RT + Vancomycin).