西湖大学最新Cell：蔡尚团队揭示肿瘤内细菌差异化调控肿瘤免疫新机制——出则为火，入则为冰

Core Viewpoint - The study reveals the dual role of intratumoral bacteria in regulating tumor immunity, highlighting the significant impact of bacterial invasion on immune responses and tumor recurrence [3][12][18]. Group 1: Tumor Microenvironment and Immune Response - Tumors are categorized as "hot" (immune-activated) or "cold" (immune-suppressive) based on immune cell infiltration and activity, with cold tumors showing insufficient immune response and resistance to immunotherapy [2]. - The presence of intratumoral bacteria is linked to regional immune-suppressive microenvironments, influencing cancer cell behavior and immune cell function through various mechanisms [2][3]. Group 2: Research Findings on Bacteria and Tumor Cells - The research conducted by Cai Shang's team demonstrates that intracellular bacteria activate the cGAS-STING-IL17B signaling pathway in cancer cells, leading to the induction of neutrophils into an immune-suppressive state, thus promoting tumor recurrence [3][12]. - In contrast, extracellular bacteria induce neutrophil subpopulations with anti-tumor functions, activating immune responses that inhibit tumor recurrence [3][12]. Group 3: Methodology and Experimental Models - A strict model for studying intracellular bacteria was established using organoid-bacteria co-culture systems, allowing for the specific investigation of the physiological functions of intracellular bacteria [8]. - In preclinical mouse models, the presence of intracellular bacteria was found to be a key factor in long-term tumor recurrence, with antibiotic treatment reducing recurrence rates significantly from 65% to 6.7% [9]. Group 4: Immune Cell Dynamics - Single-cell RNA sequencing revealed that intracellular bacteria induce neutrophils with myeloid-derived suppressor cell (G-MDSC) characteristics, while extracellular bacteria promote neutrophils with anti-tumor profiles [11][12]. - The cGAS-STING pathway is crucial for the immune reprogramming induced by bacterial invasion, with IL-17B identified as a key mediator in promoting immune suppression [12][14]. Group 5: Clinical Relevance and Future Directions - The study indicates that the strength of bacterial signals within tumor tissues correlates positively with neutrophil infiltration and is associated with poorer prognosis in breast cancer patients [15][19]. - Future research aims to explore targeted strategies for eliminating or limiting intracellular bacterial invasion, optimizing postoperative antibiotic and immunotherapy combinations to prevent tumor recurrence [19].