实体肿瘤的炎性微环境会形成类慢性炎症的促肿瘤环境，类似于顺反创伤愈合反应。我们研究了直接在肿瘤内注射微生物生物粒子改变肿瘤微环境状态从慢性炎症到急性微生物炎症的影响。肿瘤内微生物生物粒子注射可以迅速且显著地改变肿瘤免疫组成，其中最引人注目的是激活中性粒细胞的显著增加。原位光转换和体内显微镜观察显示，肿瘤中的中性粒细胞瞬时转变为高度活动的、聚集在肿瘤中形成中性粒细胞富集领域的运动中性粒细胞。中性粒细胞的簇集重塑了肿瘤组织并抑制了肿瘤生长。单细胞转录分析表明，受微生物刺激的中性粒细胞基因表达向高度激活和抗微生物效应器官移动。微生物激活的中性粒细胞也上调趋化因子，已知该趋化因子可以调节中性粒细胞和CD8+ T细胞的存在。微生物疗法还提高了CD8+ T细胞的功能，并增强了对肿瘤扫描仪治疗的治疗效果，并在肿瘤复发模型中提供保护。这些数据表明，微生物疗法的主要效应机制之一是将肿瘤中的中性粒细胞从创伤愈合转变为急性激活的细胞毒性表型，强调了更广泛地应用微生物疗法治疗实体癌症的理性。

The inflammatory microenvironment of solid tumors creates a pro-tumorigenic milieu that resembles chronic inflammation akin to a subverted wound healing response. Here we investigated the effect of converting the tumor microenvironment from a chronically inflamed state to one of acute microbial inflammation by injecting microbial bioparticles directly into tumors. Intratumoral microbial bioparticle injection led to rapid and dramatic changes in the tumor immune composition, the most striking of which was a substantial increase in the presence of activated neutrophils. In situ photoconversion and intravital microscopy indicated that tumor neutrophils transiently switched from sessile producers of vascular endothelial growth factor to highly motile neutrophils that clustered to make neutrophil-rich domains in the tumor. The neutrophil clusters remodeled tumor tissue and repressed tumor growth. Single cell transcriptional analysis of microbe-stimulated neutrophils showed a profound shift in gene expression towards heightened activation and anti-microbial effector function. Microbe-activated neutrophils also upregulated chemokines known to regulate neutrophil and CD8+ T cell recruitment. Microbial therapy also boosted CD8+ T cell function and enhanced the therapeutic benefit of checkpoint inhibitor therapy in tumor-bearing mice and provided protection in a model of tumor recurrence. These data indicate that one of the major effector mechanisms of microbial therapy is the conversion of tumor neutrophils from a wound healing to an acutely activated cytotoxic phenotype, highlighting a rationale for broader deployment of microbial therapy in the treatment of solid cancers.