Thus, tumor-infiltrating check details myeloid cells appear to be primed directly or indirectly by gut commensal bacterial LPS through the TLR4 receptor for responsiveness to the TLR9 ligand CpG-ODN. The overall composition of the fecal microbiota was also found to segregate mice that showed either high or low TNF responses to CpG-OGN. In particular, the abundance of several Gram-positive and Gram-negative bacterial species in the fecal microbiota was found to positively correlate with the response of tumor myeloid cells to CpG-ODN, whereas the abundance of certain commensal Lactobacillus species showed a negative

correlation [22]. The enhancement of the CpG-ODN response by the Gram-negative Alistipes shaii, and its attenuation by L. fermentum were directly demonstrated by in vivo association experiments [22]. In the same study, the effectiveness of the treatment https://www.selleckchem.com/products/Erlotinib-Hydrochloride.html of mouse sterile subcutaneous transplanted tumor with the platinum compounds oxaliplatin and cisplatin

was also observed to be dramatically reduced in antibiotic-treated or GF mice compared with conventional mice [22]. Platinum compounds are cytotoxic by virtue of forming platinum-DNA adducts that primarily accumulate intrastrand cross-links, and these in turn inhibit proliferation and induce apoptosis, in part by recruitment of the ataxia telangiectasia and rad3-related kinase to the DNA lesion and p53 activation [168]. In

addition to their direct cytotoxic effect, oxaliplatin but not cisplatin has been shown to induce immunogenic cell death, which releases endogenous activators of inflammation, L-gulonolactone oxidase such as high-mobility group protein B1 and ATP, thus driving activation of antigen-presenting cells and antitumor T-cell immunity [169, 170]. In antibiotic-treated mice, although the formation of platinum adducts to tumor cell DNA was not impaired, a significant decrease in DNA damage and cytotoxicity compared with conventional mice was already observed at day 2 after treatment, suggesting that antibiotics administration had suppressed the early genotoxic effect of the drug rather than the inflammatory/immune activation induced by immunogenic cell death [22]. Clear evidence suggests that H2O2 is important for the DNA damage and apoptosis induction effected by platinum compounds [171]. Antibiotics treatment was shown to inhibit the oxaliplatin-induced enhanced expression of genes related to inflammation, and in particular to monocyte differentiation, activation, and function, whereas it prevented the oxaliplatin-induced downregulation of genes related to normal cellular function, such as metabolism, transcription, translation, and DNA replication [22].