engleski

The role of NK cells in different molecular subtypes of breast cancer: friend or foe

INTRODUCTION: Breast cancer is one of the leading causes of cancer related deaths. In addition, immune infiltration of breast tumors has been shown to be related to clinical outcome. With respect to other infiltrating immune cells in breast cancer, a strong proportion of natural killer cells (NK) have been found in triple negative breast cancer. As part of the innate immunity, NK cells have a key role to control tumour growth by their cytotoxic activity. Based on this the goal of study was to investigate the immune profile of NK cells in order to gain a better understanding of pathological behaviour by different breast cancer subtypes. MATERIAL AND METHODS: Immunohistology was used to detect presence and localization of CD56 and IL-15 in paraffin embedded normal and tumoral breast tissue sections. The distribution and frequency of NKG2A, NKG2C, NKp46, CD94, CD69 and CD107a, was investigated in population of NK cells in mononuclear cell suspensions from peripheral blood by flow cytometry. Cytolitic mediatorꞌs mRNA was detected by quantitative RT-qPCR. RESULTS: The percentage of IL15+ and CD56+ cells were significantly higher in triple negative breast cancer tissue in comparison to luminal A and luminal B breast cancer. The frequency of NK cell activating receptors was decreased in breast cancer subtypes while inhibitory receptor (NKG2A) increased. This data correlated with decreased NK cell function, most notably cytotoxicity. Gene expression of cytolitic mediators at local level were up regulated in luminal B breast cancer. CONCLUSION: Our data show that modulation of NK cell activity at local and systemic level could be involved in pathogenesis of breast cancer. This highlights the importance of developing therapies that will be able to restore NK cell cytotoxicity to limit tumor escape from antitumor immunity. Acknowledgement: The experiments were financed by the grant No. 19-171498

breast cancer ; NK cells.

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