Background: The problem of elaboration of methods for effective mobilization of immune antitumor processes remains urgent. Earlier, it was shown that regression of experimental animal tumors can be achieved under the influence of low-intensive electromagnetic radiations (EMR) and magnetite nanoparticles (NPs) (Garkavi L.H. et al, 1996; 2013).The aim of the study was to determine the possibility of regression of large transplanted tumors of white rats under the influence of low-intensity EMR of millimeter range (EHF) and magnetite NPs. Methods: In experiments on 123 white outbred male rats (200-300g) with transplanted Pliss lymphosarcoma - low-intensity EMR EHF (42.2 GHz, 10 mW/cm2, exposure 15-30 min, low-frequency modulation) and magnetite NPs (10 ± 2 nm) in the form of the magnetic fluid AM-01 ("AM-Cube", Ekaterinburg) were used. The EMR acted on the animal's head starting 3 days before the tumor was transplanted. NPs were injected into peritumoral zone 2-3 times a week in a single dose of 17.7 mg/kg to animals with already formed tumors. Duration of treatment was 4 weeks. We studied the dynamics of tumor size, histochemical and cytometric changes in tumor tissue. The Wilcoxon test was used to evaluate the results. Results: When EMR EHF was used, complete regression of tumors with a size of 5-6 cm3 and a partial regression (by 30-40%) of tumors with a size of 10-13 cm3 were noted. The effect was obtained in 33% of the animals. In cases of using of magnetite NPs, tumor regression was observed in 40% of the animals, complete regression of tumors with a size of 5-30 cm3 was observed. Before the regression began, the tumor growth rates did not differ from those in the control group when using as one as the other factor. In addition, the regression was characterized by a rapid rate (5-7 days) and no signs of intoxication in animals. In the peritumoral area considerable macrophage activity and increasing number of cytotoxic T-lymphocytes were noticed. Conclusions: The timing of the onset of regression, its dynamics and the absence of signs of intoxication during rapid elimination of large tumors indicated the deployment of antigen-presentation processes and specific killing of tumor cells by inducing apoptosis. Legal entity responsible for the study: Rostov Research Institute of Oncology, Ministry of Public Healthcare of the Russian Federation Funding: Rostov Research Institute of Oncology Disclosure: All authors have declared no conflicts of interest.

Background It has previously been shown that additional local electromagnetic impact on the tumor en-hances the systemic antitumor effect of low-intensity electromagnetic radiation (EMR) used in the activation therapy regimes designed by Garkavi L.H. et al. (1990–2008). At the same time the question of the influence of weak EMR, applied to the peritumoral area, on the tumor development has not been studied. The aim of the study was to investigate the changes in the tumor caused by low-intensity microwave electromagnetic radiation of bioeffective frequency that acted on the head and peritumoral zone. Materials and methods The effects of resonance radiation (RR) with frequency corresponding to that of one of the water-containing medium radiations – 1 GHz (“SPE-effect”) – were studied on 53 adult male outbred white rats with transplantable sarcoma 45. Special anticancer agents were not used. The power flux density of RR was less than 1 μW/cm2, surface area of the emitter – 4 cm2, 3–10 min. exposure depending on algorithms of the activation therapy. RR exposure in different groups of animals was localized to the head only, or to the peri-tumoral area only, or successively to the head and peritumoral area (“double” exposure). The course lasted for 4 weeks. The exposure effect was assessed according to the dynamics of the tumor size and results of the light and electron microscopy analysis of tumor changes (JEOL JEM-1011, Japan). Results The effect of RR in different groups of animals depended on the exposure localization. Central systemic exposure was decisive. The group receiving RR localized to the head showed regression of the tumor or inhibition of its growth in 60% of animals – almost complete tumor regression in 10% and tumor growth inhibition by 70% in the rest cases. RR to the peritumoral area did not show significant influence on the tumor development, while it increased antitumor effect of the central exposure (p  μ m width. Different numbers of lymphocytes and plasma cells were noted in tumor cells. Macrophages were found. Migrating lymphocytes were often noted in the vessels among tumor cells. Electron microscopy showed multiple contacts of lymphocytes with the surface of tumor cells through cytoplasmic excrescences. Such lymphocytes had distinct signs of activation. Simultaneous contacts of lymphocytes and macrophages among themselves and with tumor cells were found. Analysis of ultrastructural characteristics of cells in regressing tumors and detection of collagen in intercellular spaces during histochemical examination of tumor tissues showed the increase in the degree of differentiation of some sarcoma 45 cells. Conclusion Possibility to increase the systemic antitumor effect of the low-intensity microwave radiation with an additional weak exposure on the peritumoral area was demonstrated for the first time. Damaging effect of RR on tumor was mediated by the changes in composition and activity of elements of the tumor’s immune microenvironment and by the increase in the degree of differentiation of some tumor cells, probably under the influence of bioactive factors of leukocytic origin.