Core Viewpoint - The study highlights the potential of the probiotic Clostridium butyricum to enhance the efficacy of anti-PD-1 therapy in colorectal cancer by inhibiting IL-6-mediated immunosuppression [3][4][6]. Group 1: Research Findings - Clostridium butyricum is identified as a probiotic that can improve the effectiveness of anti-PD-1 therapy in colorectal cancer models [6]. - The study demonstrated that Clostridium butyricum enhances tumor suppression in both microsatellite instability-high (MSI-H) and microsatellite stable (MSS) colorectal cancer models [6]. - Single-cell RNA sequencing revealed that Clostridium butyricum activates cytotoxic CD8+ T lymphocytes and inhibits tumor-associated macrophages, particularly when used in combination with anti-PD-1 therapy [6][7]. Group 2: Mechanism of Action - The surface protein secD of Clostridium butyricum binds to the receptor GRP78 on colorectal cancer cells, leading to the inactivation of GRP78 and suppression of the PI3K-AKT-NF-κB pathway, which reduces the secretion of the immunosuppressive cytokine IL-6 [7]. - IL-6 is known to inhibit cytotoxic T lymphocytes and induce tumor-associated macrophages, thus its reduction is crucial for enhancing anti-tumor immunity [7]. Group 3: Clinical Implications - The study's findings suggest that Clostridium butyricum could be a promising adjunct to immune checkpoint blockade therapies in colorectal cancer, potentially improving patient outcomes [10]. - The research establishes a foundation for the clinical application of Clostridium butyricum in enhancing anti-PD-1 therapy effectiveness [7][10].