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Updated: Aug 15, 2025

Flow Cytometry-based Assay for the Monitoring of NK Cell Functions
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Published on: October 30, 2016

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Janus kinase inhibitors alter NK cell phenotypes and inhibit their antitumour capacity

Loïc Meudec1,2, Pauline Richebé2, Juliette Pascaud1

  • 1Center for Immunology of Viral Infections and Autoimmune Diseases, INSERM UMR 1184, Université Paris-Saclay, Le Kremlin Bicêtre, Paris, France.

Rheumatology (Oxford, England)
|December 30, 2022
PubMed
Abstract

Insights

Janus kinase inhibitors (JAKi) impact natural killer (NK) cell function and antitumor activity. This study reveals that JAKi alter NK cell activation and cytotoxicity, raising questions about their role in cancer risk.

Area of Science:

  • Immunology
  • Pharmacology
  • Oncology

Background:

  • Janus kinase inhibitors (JAKi) are effective for rheumatoid arthritis (RA).
  • Concerns exist regarding cancer risk associated with JAKi use.
  • Natural killer (NK) cells play a crucial role in antitumor responses.

Purpose of the Study:

  • To investigate the impact of JAK inhibitors on NK cells in rheumatoid arthritis patients.
  • To assess the effects of specific JAK inhibitors (tofacitinib, baricitinib, upadacitinib, filgotinib) on NK cell phenotype and function.

Main Methods:

  • Ex vivo phenotyping of NK cells from RA patients treated with JAKi or methotrexate (MTX).
  • In vitro culture of NK cells from healthy donors with JAKi or DMSO.
  • Assessment of NK cell function including activation markers, cytokine production, and cytotoxicity against tumor cell lines.

Main Results:

  • JAKi treatment, particularly tofacitinib (TOFA) and upadacitinib (UPA), reduced NK cell activation markers (CD69, NKp30).
  • Tofacitinib impaired NK cell degranulation (CD107a) and cytokine production (IFN-γ/TNF) upon stimulation.
  • NK cells exposed to tofacitinib exhibited reduced cytotoxicity against A549 and SU-DHL-4 tumor cell lines.

Conclusions:

  • JAK inhibitors have a significant impact on NK cell phenotype and function.
  • These drugs impair NK cell antitumor activity, with varying effects among different JAKi.
  • The observed effects on NK cells warrant further investigation into their contribution to the increased tumor risk associated with JAKi, especially tofacitinib.
Keywords:
BiomarkersCancerJanus kinase inhibitorsNK cellsRA

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