A pan-cancer analysis of the microbiome in metastatic cancer reveals that tumor-resident bacterial DNA is detectable in a wide range of metastatic tumors. By analyzing 4,160 metastatic tumor biopsies, researchers identified organ-specific microbial tropisms, the enrichment of anaerobic bacteria in hypoxic tumors, and associations between microbial diversity and tumor-infiltrating neutrophils. Fusobacterium DNA abundance was linked to poor immunotherapy response in non-small cell lung cancer (NSCLC) patients. The study also showed that microbial communities in metastases evolve over time and can be depleted by immunotherapy. A pan-cancer resource of the metastatic tumor microbiome was generated, highlighting the associations between microbial community dynamics and tumor immunity and immunotherapy efficacy. The findings suggest that the microbiome plays a significant role in shaping tumor biology, immune infiltration, and treatment responses. The study also identified that Fusobacterium is associated with poor response to immune checkpoint blockade (ICB) in NSCLC. The results emphasize the importance of understanding the tumor microbiome in metastatic cancer to improve treatment strategies. The study provides insights into the complex interactions between the tumor microbiome and the host immune system, and highlights the potential of targeting the microbiome to enhance cancer immunotherapy. The research underscores the need for further investigation into the role of the tumor microbiome in metastatic cancer and its potential as a therapeutic target.A pan-cancer analysis of the microbiome in metastatic cancer reveals that tumor-resident bacterial DNA is detectable in a wide range of metastatic tumors. By analyzing 4,160 metastatic tumor biopsies, researchers identified organ-specific microbial tropisms, the enrichment of anaerobic bacteria in hypoxic tumors, and associations between microbial diversity and tumor-infiltrating neutrophils. Fusobacterium DNA abundance was linked to poor immunotherapy response in non-small cell lung cancer (NSCLC) patients. The study also showed that microbial communities in metastases evolve over time and can be depleted by immunotherapy. A pan-cancer resource of the metastatic tumor microbiome was generated, highlighting the associations between microbial community dynamics and tumor immunity and immunotherapy efficacy. The findings suggest that the microbiome plays a significant role in shaping tumor biology, immune infiltration, and treatment responses. The study also identified that Fusobacterium is associated with poor response to immune checkpoint blockade (ICB) in NSCLC. The results emphasize the importance of understanding the tumor microbiome in metastatic cancer to improve treatment strategies. The study provides insights into the complex interactions between the tumor microbiome and the host immune system, and highlights the potential of targeting the microbiome to enhance cancer immunotherapy. The research underscores the need for further investigation into the role of the tumor microbiome in metastatic cancer and its potential as a therapeutic target.