6. Conclusions

Researches on mouse models with transplantable tumors revealed that the intratumoral administration of the CpG-ODN and a monoclonal antibody (anti-interleukin-10 antibodies) induce hemorrhagic necrosis. This stimulatory immune response was mediated by tumor

A study published in 2013 in Science using experimental model of tumor-infiltrating myeloidderived cells on antibiotic-treated and GF mice remarkably revealed that the animals were refractory to therapy with CpG-ODN and anti-IL-10 antibody and presented low levels of TNF and cytokines required for promoting the hemorrhagic necrosis. A therapeutic response was obtained after the administration of lipopolysaccharides, a ligand for the TLR9 receptors-like.

Furthermore, study on the composition of mouse microbiota demonstrated that Alistipes shahii is positively correlated with TNF production in the tumor, whereas the abundance of Lactoba-

Thus, the research sustains the importance of the intact commensal microbiota for an optimal responses to cancer therapy required for the modulation myeloid-derived cell functions in the

Platinum salts are coordination complexes of platinum used as chemotherapeutic drugs. Cisplatin and oxaliplatin interfere with DNA repair mechanism inducing intrastrand cross-link adducts activating the proapoptotic pathways. The platinum compound effect depends also by the presence of reactive oxygen species (ROS) for an apoptotic response and DNA damage.

Lida et al. presented evidence in the same study involving CpG-ODN that the therapeutic effect of the platinum salts on transplanted subcutaneous tumor depends on the presence of mice microbiota. The authors sustained that the ROS required for the genotoxic effect of these chemotherapies are produced in vivo by inflammatory cells associated to the tumor [41].

GF mice and antibiotic treatment attenuated the pharmacological effect and reduced the

Moreover, using transgenic mice deficient for the myeloid NADPH oxidase NOX2 (Cybb\_/\_)

The study highlights the importance of commensal on an efficient therapy by its contribution

The problem of the therapeutic response variability was the starting point of recent researches which deal with the importance of microbiota in case of the patients treated with monoclonal

with a low ROS response, the effect of oxaliplatin was attenuated.

necrosis factor (TNF) and other inflammatory cytokines [40].

No response was obtained on TLR9-deficient mice [39].

cillus fermentum negatively correlated with it.

tumor microenvironment [22, 41].

128 Anti-cancer Drugs - Nature, Synthesis and Cell

expression of ROS-responsive genes.

5.4. Immune checkpoint blockade therapy

antibodies involved in the immune checkpoint blockade.

5.3. Platinum salts

to tumor reduction.

Even though there are increasing evidences regarding the close relationship between tumor development, chemotherapy, microbiota, and the immune system, it is still difficult and speculative to consider the microbes when deciding the therapeutic strategy for patients. However, modulating microbiota may enhance drug efficacy or diminish chemotherapy's toxicity.
