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Semaphorin 7A modulates cytokine-induced memory-like responses by human natural killer cells.

Publication ,  Journal Article
Ghofrani, J; Lucar, O; Dugan, H; Reeves, RK; Jost, S
Published in: Eur J Immunol
August 2019

Cytokine-induced memory-like (CIML) NK cells are endowed with the capacity to mediate enhanced effector functions upon cytokine or activating receptor restimulation for several weeks following short-term preactivation with IL-12, IL-15, and IL-18. Promising results from a first-in-human clinical trial highlighted the clinical potential of CIML NK cells as adoptive immunotherapy for patients with hematologic malignancies. However, the mechanisms underlying CIML NK cell differentiation and increased functionality remain incompletely understood. Semaphorin 7A (SEMA7A) is a potent immunomodulator expressed in activated lymphocytes and myeloid cells. In this study, we show that SEMA7A is substantially upregulated on NK cells stimulated with cytokines, and specifically marks activated NK cells with a strong potential to release IFN-γ. In particular, preactivation of NK cells with IL-12+IL-15+IL-18 resulted in greater than tenfold upregulation of SEMA7A and enhanced expression of the ligand for SEMA7A, integrin-β1, on CIML NK cells. Strikingly, preactivation in the presence of antibodies targeting SEMA7A lead to significantly decreased IFN-γ production following restimulation. These results imply a novel mechanism by which cytokine-enhanced SEMA7A/integrin-β1 interaction promotes CIML NK cell differentiation and maintenance of increased functionality. Our data suggest that targeting SEMA7A/integrin-β1 signaling might provide a novel immunotherapeutic approach to potentiate antitumor activity of CIML NK cells.

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Published In

Eur J Immunol

DOI

EISSN

1521-4141

Publication Date

August 2019

Volume

49

Issue

8

Start / End Page

1153 / 1166

Location

Germany

Related Subject Headings

  • Up-Regulation
  • Semaphorins
  • Protein Binding
  • Neoplasms
  • Lymphocyte Activation
  • Killer Cells, Natural
  • Interferon-gamma
  • Integrin beta1
  • Immunomodulation
  • Immunology
 

Citation

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Ghofrani, J., Lucar, O., Dugan, H., Reeves, R. K., & Jost, S. (2019). Semaphorin 7A modulates cytokine-induced memory-like responses by human natural killer cells. Eur J Immunol, 49(8), 1153–1166. https://doi.org/10.1002/eji.201847931
Ghofrani, Joshua, Olivier Lucar, Haley Dugan, R Keith Reeves, and Stephanie Jost. “Semaphorin 7A modulates cytokine-induced memory-like responses by human natural killer cells.Eur J Immunol 49, no. 8 (August 2019): 1153–66. https://doi.org/10.1002/eji.201847931.
Ghofrani J, Lucar O, Dugan H, Reeves RK, Jost S. Semaphorin 7A modulates cytokine-induced memory-like responses by human natural killer cells. Eur J Immunol. 2019 Aug;49(8):1153–66.
Ghofrani, Joshua, et al. “Semaphorin 7A modulates cytokine-induced memory-like responses by human natural killer cells.Eur J Immunol, vol. 49, no. 8, Aug. 2019, pp. 1153–66. Pubmed, doi:10.1002/eji.201847931.
Ghofrani J, Lucar O, Dugan H, Reeves RK, Jost S. Semaphorin 7A modulates cytokine-induced memory-like responses by human natural killer cells. Eur J Immunol. 2019 Aug;49(8):1153–1166.
Journal cover image

Published In

Eur J Immunol

DOI

EISSN

1521-4141

Publication Date

August 2019

Volume

49

Issue

8

Start / End Page

1153 / 1166

Location

Germany

Related Subject Headings

  • Up-Regulation
  • Semaphorins
  • Protein Binding
  • Neoplasms
  • Lymphocyte Activation
  • Killer Cells, Natural
  • Interferon-gamma
  • Integrin beta1
  • Immunomodulation
  • Immunology