Fc Receptor is Involved in Nk Cell Functional Anergy Induced by Miapaca2 Tumor Cell Line.

Autor: Ostapchuk, Yekaterina O., Perfilyeva, Yuliya V., Kali, Aikyn, Tleulieva, Raikhan, Yurikova, Oxana Yu., Stanbekova, Gulshan E., Karalnik, Boris V., Belyaev, Nikolai N.
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Zdroj: Immunological Investigations; Jan 2022, Vol. 51 Issue 1, p138-153, 16p
Abstrakt: Impaired NK cytotoxicity has been linked to poor cancer prognosis, but its mechanisms are not clearly established. Increasing data demonstrate that NK cells lose cytotoxicity after interaction with NK cell-sensitive tumor cells. In this paper, we provide evidence that the human adenocarcinoma cell line MiaPaCa2 and TNFα and TGFβ-treated MiaPaCa2 cultures (MiaPaCa2-TT) induced functional anergy of NK cells via FGL2 protein. MiaPaCa2-TT cultures decreased expression of IFNγ, CD107a, DNAM-1, and stimulated expression of PD1 by NK cells, as well as inhibited their cytotoxic activity in a greater manner compared to the parental culture. More importantly, we found that co-cultivation with anergized NK cells decreased expression of IFNγ and CD107a by naïve NK cells, which supports the hypothesis of NK cell functional anergy transmission. The obtained results suggest a mechanism by which tumor cells may inhibit cytotoxic functions of tumor-infiltrating and circulating NK cells in cancer. Abbreviations: CFSE: Carboxyfluorescein diacetate succinimidyl ester; CSCs: Cancer stem cells; FGL2: Fibrinogen-like protein 2; mAbs: Monoclonal antibodies; MiaPaCa2: Human adenocarcinoma cell line; MiaPaCa2-ТТ: Adenocarcinoma cell line MiaPaCa2 cells stimulated with TNFα and TGFβ-1; PI: Propidium iodide; TGFβ: Transforming growth factor beta; TME: Tumor microenvironment; TNFα: Tumor necrosis factor alfa [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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