Decreased NK cell cytotoxicity and increased T regulatory cells facilitate progression of metastatic murine melanoma

Gordana D Radosavljevic; Ivan Jovanovic; Katerina Martinova; Danijela Zivic; Nada Pejnovic; Nebojsa Arsenijevic; Miodrag L Lukic

doi:10.5937/sjecr13-1726

Gordana D Radosavljevic Univerzitet u Kragujevcu, Fakultet medicinskih nauka
Ivan Jovanovic Univerzitet u Kragujevcu, Fakultet medicinskih nauka
Katerina Martinova
Danijela Zivic Univerzitet u Kragujevcu, Fakultet medicinskih nauka
Nada Pejnovic Univerzitet u Kragujevcu, Fakultet medicinskih nauka
Nebojsa Arsenijevic Univerzitet u Kragujevcu, Fakultet medicinskih nauka
Miodrag L Lukic Univerzitet u Kragujevcu, Fakultet medicinskih nauka

DOI: https://doi.org/10.5937/sjecr13-1726

Keywords: T regulatory cells, NK cells cytotoxicity, Melanoma, Cells,

Abstract

Malignant melanoma is the most aggressive form of skin cancer. Metastatic dissemination in distant organs is the hallmarks of melanoma progression. Immunosuppression and tumor escape from immune surveillance are thought to be the major factors responsible for the establishment and progression of melanoma, however the exact mechanisms leading to decreased anti-tumor immunity are not completely understood. We aimed to analyze anti-tumor immune response during hematogenous metastasis using the B16-F1 metastatic melanoma model in C57BL/6 mice. Twenty-one days after tumor cell inoculation rapid metastatic melanoma growth was observed, reflected through increased incidence, number and size of metastatic colonies in the lungs (B16-F1). Phenotypic analyses of splenocytes revealed the increased percentage of CD3⁺T lymphocytes, markedly reduced percentage of CD19⁺ B cells and increased percentage and absolute number of CD4⁺Foxp3⁺T regulatory cells. Cytotoxic cell activity of total splenocytes and isolated NK cells were significantly decreased in tumor-bearing mice. Thus, metastatic progression of melanoma in this model is associated with diminished NK cytotoxicity which may be due to increased expansion of suppressive CD4⁺Foxp3⁺T regulatory cells in the spleen.