5.2. CpG oligodeoxynucleotides

The cytosine phosphodiester-linked guanine (CpG) oligodeoxynucleotides (CpG-ODN) are synthetic compounds with immunostimulatory effect used for enhancing the anticancer treatments. Preclinical and clinical study demonstrated a synergy between these drugs and monoclonal antibody and can be safely administrated together for a better therapeutic response [40–42].

The microbial DNA contains unmethylated cytosine phosphodiester-linked guanine (CpG) motifs which are recognized by specific immune receptors of the host-like human toll-like receptor 9 (TLR9) present on the surface of different immune cell types. Activation of these receptors enhances the expression of proinflammatory cytokines.

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

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

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 Lactobacillus fermentum negatively correlated with it.

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 tumor microenvironment [22, 41].
