We studied the effect of the HLDF differentiation factor on production of cytokines by biopsy samples of nonmalignant breast diseases (ND) and invasive breast carcinoma of no special type (IBC-NST), in the absence and presence of lymphogenic metastasis: IBC-NST patients werw subdivided into groups on the prognostic protocol of the 8th edition of the AJCC committee. Group IA consisted of patients with T1-T2 tumor sizes, and predominantly with positive expression of estrogen and progesterone receptors (ER+/PR+/HER2-); it also included one patient with the HER2+ (ER-/PR-/HER2+) molecular subtype. The IB group was mainly composed of patients with T2 tumor size, with the presence of lymphogenic metastasis (in 8 out of 10) patients and with positive expression of estrogen and progesterone receptors (ER+/PR+/HER2-) and it also included three patients with the HER2+ (ER-/PR-/HER2+) molecular subtype. Group IIA consisted of patients with T1-T2 tumor sizes, mainly with no metastases in the lymph nodes (in 11 out of 12 patients) and with a triple negative molecular subtype. Group IIB included patients with T2 tumor size, the presence of nodal metastasis and the expression of markers of ER-/PR-/HER2 - and ER-/PR-/HER2+. Group IIIA consisted of patients with tumor size T1-T3, with the presence of nodal metastasis and the expression of markers of ER-/PR+/HER2+ and ER-/PR-/HER2+. Group IIIC consisted of patients with T3 tumor size, lymphogenic metastasis, and expression of ER-/PR-/HER2-markers (triple negative molecular subtype). Due to a limited number of patients in the groups IIB, IIIA and IIIC, as well as due to more severe clinical and pathological stages, according to the prognostic Protocol of the 8th edition of the AJCC Committee, they were pooled into group III. Concentrations of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 were assayed in supernatants of biopsy specimens of breast tissue. Results have shown that with IBC-NST, a statistically significantly higher level of spontaneous production (SP) by biopsy specimens of IL-17, IL-18, IFN-γ and VEGF, and a lower level of SP IL-6 as compared with ND. Patients of all clinical and pathological groups showed a high VEGF spontaneous production as compared with ND, while statistically significant differences from patients with ND were not found in IL-17 spontaneous production in group IB patients, and IL-18 spontaneous production were absent in group IA. Only in patients with IA and IB, the IL-6 spontaneous production was lower as compared to ND, and the IL-8 spontaneous production was lower in the IA group. IFN-γ spontaneous production was higher in patients with IBC-NST group IIA as compared with ND. Under the influence of the HLDF differentiation factor, it was found that the parameters of IBC-NST patients were statistically significantly higher in the production of IL-1Ra, IL-17, IL-18 and VEGF, and statistically significantly lower in the production of IL-6 as compared to ND. HLDF had a higher impact on the content of IL-18 in IBC-NST patients than in ND. After HDLF sublimation IL-6 values were lower in patients of groups IA and IB, and HLDF-induced IL-17 production was higher only in patients of group IA. Statistically significant differences in the index of influence of HLDF (IVHLDF), representing ratio of the cytokine concentration in the supernatants of a biopsy specimen stimulated by HLDF to spontaneous cytokine production, were found between ND and IBC-NST in the case of on IFN-γ production, and also in the case of IL-4 production (between patients in the absence and presence of lymphogenic metastasis). IVHLDF for production of IL-6, IL-8 and TNF-α was lower in group IIA patients compared to group IA, and IVHLDF for production of GM-CSF and MCP-1 was lower in group IIA as compared to group III, in addition IVHLDF for MCP-1 products was lower in group IIA as compared to ND. The HLDF effect on the cytokine production by the tumor and its microenvironment was different in ND patients and IBC-NST patients. HDLF suppressed IFN-γ production in the pooled group of IBC-NST patients; HLDF mainly had a suppressive effect on the production of IL-6, IL-8, TNF-α, GM-CSF and MCP-1 in IBC-NST patients of group IIA.Issledovali vliianie faktora differentsirovki HLDF na produktsiiu tsitokinov bioptatami pri nezlokachestvennykh zabolevaniiakh molochnoĭ zhelezy (NZ) i pri invazivnoĭ kartsinome molochnoĭ zhelezy nespetsificheskogo tipa (IKNT), pri otsutstvii i nalichii limfogennogo metastazirovaniia, a takzhe u patsientov s IKNT, raspredelennykh po podtipam na osnove prognosticheskogo protokola 8 izdaniia komiteta AJCC. Gruppu IA sostavili patsienty s razmerami opukholi T1-T2 i preimushchestvenno s polozhitel'noĭ ékspressieĭ retseptorov éstrogena i progesterona (ER+/PR+/HER2-) i odin patsient s HER2+ (ER-/PR-/HER2+) molekuliarnym podtipom. V gruppu IB byli vkliucheny patsienty s razmerami opukholi T2, preimushchestvenno s nalichiem limfogennogo metastazirovaniia (8 iz 10) i s polozhitel'noĭ ékspressieĭ retseptorov éstrogena i progesterona (ER+/PR+/HER2-), a takzhe tri patsienta s molekuliarnym podtipom HER2+ (ER-/PR-/HER2+). Gruppu IIA sostavili patsienty s razmerami opukholi T1-T2, preimushchestvenno s otsutstviem metastazov v limfouzlakh (11 iz 12 bol'nykh) i s troĭnym negativnym molekuliarnym podtipom. Gruppu IIB sostavili patsienty s razmerami opukholi T2, nalichiem limfogennogo metastazirovaniia i ékspressieĭ markerov: ER-/PR-/HER2- i ER-/PR-/HER2+. Gruppu IIIA sostavili patsienty s razmerami opukholi T1-T3, nalichiem limfogennogo metastazirovaniia i ékspressieĭ markerov: ER-/PR+/HER2+ i ER-/PR-/HER2+. Gruppu IIIC sostavili patsienty s razmerami opukholi T3, s nalichiem limfogennogo metastazirovaniia i s ékspressieĭ markerov ER-/PR-/HER2- (troĭnoĭ negativnyĭ molekuliarnyĭ podtip). Vvidu malogo kolichestva patsientov v gruppakh IIB, IIIA i IIIC, a takzhe v sviazi s bolee tiazhelymi kliniko-patologicheskimi stadiiami soglasno prognosticheskomu protokolu 8 izdaniia komiteta AJCC oni byli ob"edineny v odnu gruppu III. Kontsentratsii IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL- 1β, IL-1Ra TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF i MCP-1 opredeliali v supernatantakh bioptatov tkani molochnoĭ zhelezy. Issledovaniia pokazali, chto pri IKNT otmechalsia statisticheski znachimo bolee vysokiĭ uroven' spontannoĭ produktsii (SP) IL-17, IL-18, IFN-γ i VEGF i bolee nizkiĭ uroven' SP IL-6 po sravneniiu s NZ molochnoĭ zhelezy. U patsientov vsekh kliniko-patologicheskikh grupp IKNT otmechena vysokaia SP VEGF po sravneniiu s NZ, togda kak statisticheski znachimye razlichiia ot patsientov s NZ po SP IL-17 otsutstvovali u patsientov gruppy IB, a po SP IL-18 otsutstvovali u patsientov IA. Tol'ko u patsientov grupp IA i IB SP IL-6 byla nizhe po sravneniiu s NZ, a SP IL-8 byla nizhe u patsientov gruppy IA. SP IFN-γ byla vyshe u patsientov s IKNT gruppy IIA po sravneniiu s NZ. Pri vozdeĭstvii faktora differentsirovki HLDF ustanovleno, chto pokazateli patsientov s IKNT byli statisticheski znachimo bolee vysokimi po produktsii IL-1Ra, IL-17, IL-18 i VEGF i statisticheski znachimo bolee nizkimi po produktsii IL-6 po sravneniiu s NZ molochnoĭ zhelezy. Pri vozdeĭstvii HLDF na produktsiiu IL-18 ego soderzhanie okazalos' vyshe u patsientov vsekh kliniko-patologicheskikh grupp po sravneniiu s patsientami s NZ. Po sravneniiu s NZ tol'ko u patsientov grupp IA i IB pokazateli IL-6 pri vozdeĭstvii HLDF byli nizhe, a indutsirovannaia HLDF produktsiia IL-17 byla vyshe tol'ko u patsientov gruppy IA. Statisticheski znachimye razlichiia po indeksu vliianiia HLDF (IVHLDF), predstavliaiushchim soboĭ otnoshenie kontsentratsii tsitokinov v supernatante bioptata, pri vozdeĭstvii HLDF k spontannoĭ produktsii tsitokinov byli ustanovleny mezhdu NZ i IKNT po IVHLDF na produktsiiu IFN-γ, a takzhe po IVHLDF na produktsiiu IL-4 mezhdu patsientami pri otsutstvii i nalichii limfogennogo metastazirovaniia. IVHLDF na produktsiiu IL-6, IL-8 i TNF-α byl nizhe u patsientov gruppy IIA po sravneniiu s gruppoĭ IA, a IVHLDF na produktsiiu GM-CSF i MCP-1 byl nizhe u gruppy IIA po sravneniiu s pokazateliami gruppy III, krome togo, IVHLDF na produktsiiu MCP-1 byl nizhe u gruppy IIA po sravneniiu s NZ. Vliianie faktora differentsirovki HLDF na produktsiiu tsitokinov opukhol'iu i ee mikrookruzheniem razlichno dlia patsientov s NZ i IKNT. Faktor differentsirovki okazyval supressiruiushchee vliianie na produktsiiu IFN-γ u patsientov s IKNT i na produktsiiu IL-4 tol'ko u patsientov s limfogennym metastazirovaniem i na produktsiiu IL-6, IL-8, TNF-α, GM-CSF i MCP-1 u patsientov s IKNT gruppy IIA.