A18

Abstract

Tumor-associated neutrophils (TANs) are the cell population that differs in morphofunctional characteristics from peripheral blood cells (Gregory and Houghton, 2011). The first study to identify the presence of TANs as an independent poor prognostic factor and to include TANs into a prognostic risk model was published in 2006 (Donskov , 2006). Specific signals during cancer progression have been shown to induce the emergence of a pro-tumor phenotype of neutrophils (PMN). Frinlender (2013) points out an anti-tumor phenotype of TANs. Of particular interest is the study of interaction of neutrophils with T cells because the latter are considered to be cytotoxic cells mediating antitumor immunity. The aim of the study was to assess the lymphoid cell infiltration (LCI) and the functional status of TANs in ovarian cancer. LCI was assessed by immunohistochemistry and the levels of mieloproxydase (MPO) and cationic proteins (CP) were evaluated by cytochemical methods in ovarian carcinoma surgical resection specimens. The results were presented as a mean cytochemical coefficient (MCC). The intensity of nitroblue tetrazolium (NBT) test was expressed as a percentage. Obtained results were analyzed by nonparametric statistical methods. The Kruskal–Wallis test was used to evaluate the differences between groups.

We established that low intensity of infiltration in general and formation of marginal lymphoid cell ridge in some tumors are typical for malignant ovarian neoplasms. More intensive infiltration was found in the regions of the rapid growth of tumor cells, i.e. invasion zone. In some cases, a group of tumor cells was separated from the main part of the parenchyma and surrounded by lymphoid elements. Conditions are created under which active spread of cancer cells in the parenchyma is associated with intensive lymphoid cells infiltration in the stroma. Total count and density of lymphoid cells can significantly vary: from single lymphoid elements uniformly scattered in the tumor tissue to focal accumulations. In tumor tissue location of lymphoid cells is irregular, so most of the infiltration is in the stroma and among the cancer cells only solitary lymphocytes are found. Lymphoid cells which make up the infiltration include 12.3 ± 1.52% of macrophages, 22.1 ± 2.3% of plasma cells, 62.5 ± 1.1% of lymphocytes and 3.1 ± 0.9% of PMN. Total amount of cells was 224.1 ± 32.8 per 1 mm² of tumor.

Lymphocytes in ovarian carcinomas do not form large clusters; they are disposed among other lymphoid cells in the stroma on the periphery of the tumor. Plasma cells have a classical morphological structure and often locate in the stroma and on the periphery of the tumor. Macrophages are an integral part of the tumor infiltrate. In the tumor they become stretched and angular. Macrophages usually have large dimensions, and they are located in the stroma as well as in the parenchyma among the cancer cells. Segmented leukocytes (presented in the vast majority by neutrophils) are constantly found in the infiltrate of the stroma and the parenchyma, most often they are found near or among massive necrosis.

Analysis of TANs functional activity in comparison with the peripheral blood neutrophils has shown that MPO activity elevated and amounted 2.21 ± 0.43 MCC against 1.40 ± 0.07 MCC in the peripheral blood neutrophils, the level of CP also increased and amounted 1.51 ± 0.39 MCC against 0.83 ± 0.43 MCC. TANs activity in NBT-test was not significantly different from that of the peripheral blood neutrophils.

TANs compose the minor part of primary ovarian tumor infiltrate. Indicators of aerobic and anaerobic bactericidal activity of TANs significantly exceed that of the peripheral blood neutrophils in patients with ovarian cancer.

This work was conducted in the framework of implementing the state assignment of the Ministry of Education and Science of the Russian Federation No. 1163 – Russia.