Chumak A. The functional polarization of macrophages by the influence of B. subtilis IMV B-7724 lectin in setting of growth of histogenetically different tumors (experimental study)

The dissertation is devoted to the analysis of B. subtilis IMV B-7724 lectin influence on the Mph functional polarization during the growth of histogenetically different tumors as well as to the justification of the feasibility of lectin application in the development of new approaches to antitumor immunotherapy. During the growth of experimental tumors of different histogenesis (Lewis lung carcinoma (LLC) and Ehrlich adenocarcinoma (EAC)), there was noticed the change of polarization state from M1 (latent growth stage) to M2 (terminal stage) in Mph isolated from different anatomical niches. At the initial stage of LLC and EAC growth, regardless of their histogenetic origin, Mph could be characterized as M1 that is evidenced by a significant increase in the ratio of NO production to Arginase activity (NO/Arg) compared with the intact mice Mph as well as by maintenance of their cytotoxic activity and superoxide radicals production on the level of the intact mice Mph. In the terminal stage of EAC growth, there was detected a significant decrease in some indicators in peritoneal and spleen Mph activity compering with the intact mice Mph as well as a decline in tumor-associated Mph indicators comparing to data on day 14 of tumor growth. B. subtilis IMV B-7724 lectin was used as a compound possessing immunomodulatory and antitumor properties. It was observed that B. subtillis IMV B-7724 lectin showed cytotoxic activity against tumor cells of different histogenesis in vitro and also demonstrated antitumor activity in vivo. The feasibility of using B. subtillis IMV B-7724 lectin to modulate the functional polarization of Mph in normal conditions and during tumor growth was proved in vitro and in vivo, and its effectiveness in the antitumor immunotherapy was substantiated. The peculiarities of Mph functional polarization in the growth dynamics of histogenetically different experimental tumors have been identified. The most significant changes in the Mph polarization (in the M1 → M2 direction) were found during the terminal growth phase of LLC and EAC tumors. Under the influence of immunomodulatory concentrations of the lectin, there was observed a significant increase in the NO/Arg ratio towards the increase in NO production, which is characteristic of M1 phenotype Mph and increase in STAT1/STAT6 mRNA expression ratio (components of JAK-STAT signaling pathway) in Mph which is comparable with those induced by combined action of LPS and IFN-γ