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Cytokine production by blood immune cells, tumor and its microenvironment, characteristic of extracellular matrix in patients with invasive ductal carcinoma of no special type

2019; Volume: 65; Issue: 5 Linguagem: Inglês

10.18097/pbmc20196505424

2310-6972

A. I. Autenshlyus, К. И. Давлетова, А. А. Студеникина, E. S. Mikhaylova, Н. А. Вараксин, I.P. Zhurakovsky, А. В. Проскура, С. В. Сидоров, V. V. Lyakhovich,

Cancer Immunotherapy and Biomarkers

The aim of this research was to study cytokine production by blood immune cells, tumor, and its microenvironment, and characterize extracellular matrix of patients with invasive ductal carcinoma of no special type and lymphatic metastases. Spontaneous and polyclonal activators stimulated production of cytokines by blood immune cells, tumor and its microenvironment were studied in 95 patients with invasive ductal carcinoma of no special type. The concentration 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 was determined by the solid-phase enzyme-linked immunosorbent assay. The condition of fibrous component and presence of neutral glycoproteins and sulfated glycosaminoglycans were evaluated during the research of extracellular matrix. Regional lymphatic metastases were detected in 35 of 95 patients. It was shown that in the presence or absence of lymphatic metastases index of polyclonal activators influence on the production of cytokines by blood immune cells was different for IL-6, IL-8, and IL-1β; while in the case of cytokine production by tumor and its microenvironment the index of influence was different for IL-2 and IL-17. The presence of lymphatic metastases corresponded with the rise of cytokines spontaneous production, while the absence of lymphatic metastases corresponded with the rise of cytokines production stimulated by polyclonal activators. The value of indices of polyclonal activators influence on the production of cytokines by blood immune cells pointed to the highly stimulating effect of polyclonal activators while the value of indices of polyclonal activators influence on cytokines production by tumor and its microenvironments pointed to the low and sometimes even absent effect of polyclonal activators. Basing on these data we propose a ratio of indices of polyclonal activators influence for the better evaluation of the probability of lymphatic metastases during preoperative period. After characterizing extracellular matrix we found out a point threshold, which, in 100% of cases, predicted the presence of lymphatic metastases basing on the condition of extracellular matrix. Using the data acquired, we are proposing a risk group for metastasis among women with no lymphatic metastases in the moment of check-up.Issledovali spontannuiu i stimulirovannuiu poliklonal'nymi aktivatorami produktsiiu tsitokinov immunokompetentnymi kletkami krovi, opukhol'iu i ee mikrookruzheniem, a takzhe sostoianie vnekletochnogo matriksa u 95 patsientok s invazivnoĭ kartsinomoĭ molochnoĭ zhelezy nespetsificheskogo tipa pri limfogennom metastazirovanii. S pomoshch'iu immunofermentnogo analiza opredeliali kontsentratsiiu 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. Pri izuchenii vnekletochnogo matriksa otsenivali sostoianie voloknistogo komponenta, soderzhanie neĭtral'nykh glikoproteinov i sul'fatirovannykh glikozaminoglikanov. Metastazy v regionarnye limfaticheskie uzly prisutstvovali u 35 iz 95 patsientok. Issledovanie pokazalo, chto pri nalichii ili otsutstvii limfogennogo metastazirovaniia indeks vliianiia poliklonal'nykh aktivatorov na produktsiiu tsitokinov immunokompetentnymi kletkami krovi razlichalsia po trem pokazateliam (IL-6, IL-8 i IL-1β), a indeks vliianiia poliklonal'nykh aktivatorov na produktsiiu tsitokinov kletkami opukholi i ee mikrookruzheniia po dvum (IL-2 i IL-17). Nalichiiu limfogennykh metastazov sootvetstvovalo povyshenie spontannoĭ produktsii tsitokinov, a ikh otsutstviiu – povyshenie produktsii, stimulirovannoĭ poliklonal'nymi aktivatorami. Znacheniia indeksov vliianiia poliklonal'nykh aktivatorov na produktsiiu tsitokinov immunokompetentnymi kletkami krovi svidetel'stvovali o vysokom stimuliruiushchem éffekte poliklonal'nykh aktivatorov, a znacheniia indeksov vliianiia poliklonal'nykh aktivatorov na produktsiiu tsitokinov kletkami opukholi i ee mikrookruzheniia – o nizkom i dazhe otsutstvuiushchem éffekte poliklonal'nykh aktivatorov. Na osnovanii poluchennykh dannykh bylo sostavleno sootnoshenie indeksov vliianiia poliklonal'nykh aktivatorov dlia otsenki veroiatnosti limfogennogo metastazirovaniia v dooperatsionnom periode. Pri otsenke sostoianiia vnekletochnogo matriksa byl vyiavlen porog, kotoryĭ v 100% sluchaev pokazal sootvetstvie sostoianiia vnekletochnogo matriksa nalichiiu metastazov v regionarnykh limfaticheskikh uzlakh. Na osnovanii poluchennykh rezul'tatov byla predlozhena gruppa riska po metastazirovaniiu sredi zhenshchin, ne imeiushchikh na moment issledovaniia metastazov v limfaticheskikh uzlakh.