Microbiome Modulation as a Strategy to Enhance Immunotherapy in Metastatic CRC 9079

Abstract Description Therapeutic advances in the treatment of metastatic colorectal cancer (CRC) remain challenging due to treatment resistance and poor patient outcomes, especially in advanced- stage disease. CRC is the second leading cause of cancer-related mortality worldwide, with metastases significantly worsening patient outcomes. Current treatment limitations result in high recurrence rates, highlighting the urgent need for novel therapeutic approaches, particularly for advanced-stage disease. This highly-translational research focuses on exploring new treatment strategies by investigating the tumor-immune-microbiome axis. Utilizing a pre-clinical murine organoid-derived model of metastasizing, non-immunogenic CRC, we examine the impact of fecal microbiome transplantation (FMT) on enhancing the efficacy of cancer immunotherapy (CI). By performing sequential experiments, using samples from human CI responder and non-responder patients, we aim to examine how FMT shapes anti-tumor immunity, connecting these findings with clinical outcomes. Preliminary results indicate that FMT from CI-responders, when combined with CI, is associated with reduced primary tumor size and a lower metastatic burden compared to non-FMT-treated controls. These findings suggest that the gut microbiome plays a key role in the progression and therapeutic response of late-stage CRC, offering potential new avenues for treatment development, which could benefit millions of patients worldwide. Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)