The two types of immune microenvironment of renal cancer

Background. The tumor microenvironment can both restrain tumor growth and promote disease progression. Therefore, the study of tumor-infiltrating lymphocytes (TILs) subpopulation composition is an urgent and significant topic.

Aim. To characterize the immune microenvironment of renal cancer by flow cytometry.

Materials and methods. The study included blood, kidney tumor and normal tissue of the removed kidney of 32 patients with clear cell renal cancer treated at N. N. Blokhin National Medical Research Center of Oncology. Kidney tissue was obtained during surgical removal of the tumor (resection / nephrectomy). A fragment of tumor and normal tissue was taken for analysis under the control of a morphologist. Blood for the study was taken on the day of surgery. Immunologic study was performed by flow cytometry. Kidney tissue was preliminarily homogenized and cell suspension was stained, as well as peripheral blood, with monoclonal antibodies to CD45, CD3, CD4, CD8, CD16⁺CD56⁺, CD19, CD28, CD279, CD11b labeled with different fluorochromes.

Results. T-lymphocytes and natural killer (NK) cells have a pronounced inverse correlation, which allowed us to distinguish two (n = 32; 18 / 14) variants of tumor immune microenvironment. T-cell variant, with predominance of CD3⁺CD8⁺ cells over CD3⁺CD4⁺ lymphocytes, and NK cell variant – increase in the number of NK cells with a pronounced decrease in the proportion of T-lymphocytes at the expense of CD3⁺CD8⁺ lymphocytes. The two variants are based on the difference of effector link – predominance of cells of innate (NK) or adoptive (CD3⁺CD8⁺) immunity. TILs immune profiles also differed in the number of CD8⁺PD1⁺ cells – in the T-cell variant their number was 2 times higher than in the NK cell variant. The similar distribution concerned CD4⁺ Treg cells.

Conclusion. Two immunologically competitive variants of renal tumor microenvironment were revealed – T-cell variant, characterized by a greater degree of infiltration and concentration of T-regulatory cells; NK cell variant, with an insignificant degree of infiltration and a pronounced strengthening of the effector link in the tissue and proinflammatory activity of peripheral blood.

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