PROSPECTS FOR USING THE PHENOMENON OF MACROPHAGES PLASTICITY TO EVALUATE THE EFFICIENCY OF CANCER THERAPY
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine, Kyiv, Ukraine
Objectives: determination of indicators of the functional activity of peritoneal macrophages: rats with Walker-256 carcinosarcoma under various regimens of antitumor therapy and assessment of the participation of macrophages in the implementation of the antitumor effect. Object and methods: the study was conducted in Wistar rats. Walker 256 carcinosarcoma was used as a tumor growth model. For the treatment of animals doxorubicin or cisplatin were used both in monotherapy and in combined regimens with the xenogeneic antitumor vaccine (XAV). The XAV was prepared according to the method on the basis of antigens of chicken embryonic tissue and protein-containing metabolite of B. subtilis 7025 with molecular mass 70 kDa. The characteristics of tumor growth and functional activity of peritoneal macrophages were evaluated on day 24. Results: according to tumor growth characteristics, the most effective was the combined application of XAV + doxorubicin. The animals of this group were characterized by a decrease in tumor size comparing with XAV group (by 4.4 times, p < 0.05), XAV + cisplatin) (by 1.9 times). On day 24 of the tumor growth in non-treated animals, type M2 macrophages predominated; chemotherapy and/or immunotherapy led to increase of type M1 macrophages that was supported by a significant increase in nitric oxide (NO) production and a decrease in arginase activity. The most effective was the combination XAV + doxorubicin: NO level increased by 1.6 and arginase activity decreased by 1.5 times (p < 0.05 for both parameters compared with XAV group). Cisplatin application both in monotherapy, and in the combination with XAV did not exert the similar effect. Conclusions: the most pronounced antitumor efficacy in Walker 256 carcinosarcoma model was seen at application of the combined chemotherapy and immunotherapy (regimen XAV + doxorubicin). This effect was probably due to a significant increase in the amount of of type M1 macrophages, which exhibit antitumor properties. The strong negative correlation between tumor size and macrophages functional activity with the M1 phenotype indicates a significant role for these cells in inhibiting tumor growth.