Histological and immunohistochemical evaluation of tissues from immunodeficient mice with of tumor xenografts following administration of human NK cells

Immuno-oncology is an actively developing area of applied research that has revolutionized cancer treatment. In particular, NK cells are classified as cytotoxic lymphocytes that play a crucial role in recognizing and eliminating malignant or infected cells. The aim of the study was to perform a histological and immunohistochemical evaluation of human tumor xenografts (human pancreatic cancer) and internal organs of immunodeficient mice following the administration of a human NK cell suspension. Material and methods . Previously, xenografts were modeled on 4 NBSGW mice by subcutaneous administration of ASPC-1 tumor cells (human pancreatic cancer). On day 24 of the study, the animals were injected with NK cell suspension intravenously in the amount of 8.8 million and 9.2 million to mice №2 and №4, and subcutaneously in the amount of 10 million and 14 million NK cells to mice №1 and №3, respectively. On day 28 of the study, the animals were euthanized and pathomorphologically examined. Routine histological assessment of the internal organs of the mice, immunohistochemistry of xenograft samples for the presence of tumor cells with Cytokeratin 7 and Pan-Cytokeratin antibodies, as well as xenografts and internal organs of mice for the presence of CD56+ cells were performed. Results . The histoarchitecture of organs and tissues in animals was preserved, metastases were found in the lungs, no infiltration of CD56+ cells in this area of the lung tissue was noted. Single weakly positive CD56+ cells were observed in the xenografts, the membrane staining of which was barely visible. In the spleen, CD56+ cells were single, and part of the xenograft and spleen vessels (peripheral nerve fibers, pericytes) were also brightly stained. In the xenograft samples, small-droplet dystrophy of oncocytes, inflammatory infiltration and the cell renewal index were visualized less than or equal to 1.0, which together indicates mild changes in the tumor structure. Conclusion . The therapeutic effect of the NK cell suspension increases tumor pathomorphism, the areas of necrosis increase, while the cell renewal coefficient index decreases, but further studies are needed with an increase in the dose or frequency of administration.