Commensal bacteria influence cancer therapy outcomes by modulating the tumor microenvironment. A study shows that disrupting the microbiota impairs responses to immunotherapy and chemotherapy in mice. In antibiotic-treated or germ-free mice, tumor-infiltrating myeloid cells responded poorly to therapy, resulting in reduced cytokine production and tumor necrosis after CpG-oligonucleotide treatment and deficient reactive oxygen species (ROS) and cytotoxicity after chemotherapy. These findings suggest that an intact microbiota is essential for optimal cancer therapy, as it modulates myeloid cell functions in the tumor microenvironment. The gut microbiota affects inflammation and immunity, both locally and systemically, and may influence inflammatory processes contributing to cancer and its treatment. Tumor-associated inflammatory cells promote cancer cell proliferation and suppress antitumor immunity. Anticancer treatments alter this microenvironment, potentially evoking tumor-destructive immune responses. However, the role of commensal bacteria in this process remains unclear. To investigate whether commensal bacteria alter inflammation in the tumor microenvironment, mice were treated with an antibiotic cocktail (ABX) and analyzed for tumor growth and response to immunotherapy. ABX treatment reduced the frequency of certain immune cells in tumors and impaired the effectiveness of immunotherapy. ABX also reduced TNF production and other inflammatory responses in tumors. These effects were reversed by restoring the microbiota with bacterial lipopolysaccharide (LPS) or specific bacterial species. The study also found that the microbiota influences the response to chemotherapy, such as oxaliplatin. ABX treatment reduced the effectiveness of oxaliplatin, likely by impairing ROS production in tumor-associated myeloid cells. This effect was partially reversed by restoring the microbiota or by inhibiting ROS production with antioxidants. The study highlights the importance of the microbiota in cancer treatment, as it modulates the tumor microenvironment and influences the effectiveness of both immunotherapy and chemotherapy. The findings suggest that manipulating the gut microbiota could improve cancer treatment outcomes.Commensal bacteria influence cancer therapy outcomes by modulating the tumor microenvironment. A study shows that disrupting the microbiota impairs responses to immunotherapy and chemotherapy in mice. In antibiotic-treated or germ-free mice, tumor-infiltrating myeloid cells responded poorly to therapy, resulting in reduced cytokine production and tumor necrosis after CpG-oligonucleotide treatment and deficient reactive oxygen species (ROS) and cytotoxicity after chemotherapy. These findings suggest that an intact microbiota is essential for optimal cancer therapy, as it modulates myeloid cell functions in the tumor microenvironment. The gut microbiota affects inflammation and immunity, both locally and systemically, and may influence inflammatory processes contributing to cancer and its treatment. Tumor-associated inflammatory cells promote cancer cell proliferation and suppress antitumor immunity. Anticancer treatments alter this microenvironment, potentially evoking tumor-destructive immune responses. However, the role of commensal bacteria in this process remains unclear. To investigate whether commensal bacteria alter inflammation in the tumor microenvironment, mice were treated with an antibiotic cocktail (ABX) and analyzed for tumor growth and response to immunotherapy. ABX treatment reduced the frequency of certain immune cells in tumors and impaired the effectiveness of immunotherapy. ABX also reduced TNF production and other inflammatory responses in tumors. These effects were reversed by restoring the microbiota with bacterial lipopolysaccharide (LPS) or specific bacterial species. The study also found that the microbiota influences the response to chemotherapy, such as oxaliplatin. ABX treatment reduced the effectiveness of oxaliplatin, likely by impairing ROS production in tumor-associated myeloid cells. This effect was partially reversed by restoring the microbiota or by inhibiting ROS production with antioxidants. The study highlights the importance of the microbiota in cancer treatment, as it modulates the tumor microenvironment and influences the effectiveness of both immunotherapy and chemotherapy. The findings suggest that manipulating the gut microbiota could improve cancer treatment outcomes.