Ckіvka L. Immunomodulatory effects of bacterial biopolymers under the tumor growth.

Thesis deals with the mechanisms of the immunomodulatory and adjuvant action of bacterial biopolymers. In the experiments in vitro we have shown that all of PAMPs used in the investigation induced functional maturation of monocyte-derived dendritic cells (MDDC). It was observed that PAMPs with lipid constituent caused more expressed phenotypic maturity of dendritic cells. There was a synergistic effect of combined use of different TLR-agonists in stimulation of MDDC maturation, most expressed in the case of microbe-associated molecules with different signaling pathway. The characteristics of immunomodulatory potential of bacterial biopolymers under the growth of tumors with different biological properties were also investigated. Antineoplastic efficacy of bacterial macromolecules depended on the degree of immunogenicity of tumor cells. Tumor growth inhibition was associated with intensive infiltration of tumor tissue with F4/80+ macrophages, an increase in type 1 cytokine levels and significant decrease of IL10 level in tumor tissue. The synergistic immunomodulatory effect of endogenous (HMGB1) and exgenous (PAMPs) alarmins under the tumor growth was also registered. Bacterial biopolymers in combination with cytotoxic drug NSC631570 repolarized arginine metabolism of alternatively polarized hypoxic macrophages and activated their pro-inflammatory functions.