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

Yekaterina O Ostapchuk1, Yuliya V Perfilyeva1, Aikyn Kali1,2

  • 1Laboratory of Molecular Immunology and Immunobiotechnology, M.A. Aitkhozhin's Institute of Molecular Biology and Biochemistry, Almaty, Kazakhstan.

Immunological Investigations
|September 1, 2020
PubMed

Insights

Tumor cells induce NK cell anergy via FGL2 protein, impairing their cancer-fighting ability. This functional anergy can be transmitted to other NK cells, suggesting a novel tumor immune evasion mechanism.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular Mechanisms

Background:

  • Impaired Natural Killer (NK) cell cytotoxicity is associated with poor cancer prognosis.
  • Mechanisms underlying NK cell dysfunction in the tumor microenvironment (TME) are not fully understood.
  • NK cells can lose cytotoxicity upon interaction with sensitive tumor cells.

Purpose of the Study:

  • To investigate the role of Fibrinogen-like protein 2 (FGL2) in mediating NK cell functional anergy.
  • To elucidate the impact of specific tumor cell treatments (TNFα and TGFβ) on NK cell function.
  • To explore the potential transmission of NK cell functional anergy.

Main Methods:

  • Co-cultivation of NK cells with human adenocarcinoma cell line MiaPaCa2 and TNFα/TGFβ-treated MiaPaCa2 (MiaPaCa2-TT) cultures.
  • Analysis of NK cell surface markers (e.g., PD1) and cytokine production (e.g., IFNγ) via flow cytometry.
  • Assessment of NK cell cytotoxic activity and functional anergy transmission through co-culture experiments.

Main Results:

  • MiaPaCa2-TT cultures induced NK cell functional anergy, characterized by decreased IFNγ, CD107a, DNAM-1 expression, and increased PD1 expression.
  • FGL2 protein was identified as a mediator of this NK cell anergy induction.
  • Anergized NK cells were capable of decreasing IFNγ and CD107a expression in naïve NK cells, indicating transmission of anergy.

Conclusions:

  • Tumor cells, particularly when stimulated with TNFα and TGFβ, can induce functional anergy in NK cells through FGL2.
  • This FGL2-mediated anergy impairs NK cell cytotoxic functions within the tumor microenvironment.
  • The findings suggest a novel mechanism for tumor immune evasion involving the transmission of NK cell functional anergy.
Keywords:
FGL-2Natural killer cellscytotoxicityfunctional anergypancreatic adenocarcinoma MiaPaCa2

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