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HMGN2: An Antitumor Effector Molecule of γδT Cells

Jiao Chen1, Yaping Fan, Bomiao Cui

  • 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Journal of Immunotherapy (Hagerstown, Md. : 1997)
|February 6, 2018
PubMed

Insights

High mobility group nucleosomal-binding domain 2 (HMGN2) is expressed by activated gamma delta T cells and functions as an antitumor effector molecule. This finding reveals HMGN2 as a potential target for novel cancer immunotherapies.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Gamma delta T (γδT) cells play a role in regulating T-cell activation in cancer and are a target for immunotherapy.
  • Activated γδT cells release cytotoxic molecules to eliminate target cells.
  • High mobility group nucleosomal-binding domain 2 (HMGN2) is known as an antitumor effector molecule in CD8T cells.

Purpose of the Study:

  • To investigate the expression and antitumor effects of HMGN2 in γδT cells.
  • To determine if HMGN2 contributes to the cytotoxic function of γδT cells.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with isopentenyl pyrophosphate (IPP) and interleukin-2 (IL-2) to activate and expand γδT cells.
  • HMGN2 expression was quantified using flow cytometry and ELISA.
  • Cytotoxic effects were assessed using carboxyfluorescein succinimidyl ester (CFSE) labeling and blocking with anti-HMGN2 antibodies.

Main Results:

  • IPP and IL-2 effectively induced γδT cell activation and expansion in vitro.
  • HMGN2 was constitutively expressed in γδT cells and highly expressed upon IPP activation, detected both intracellularly and in the supernatant.
  • Supernatants from activated γδT cells demonstrated tumor cell-killing activity, which was inhibited by anti-HMGN2 antibodies.

Conclusions:

  • HMGN2 is constitutively expressed in γδT cells and released upon activation.
  • HMGN2 acts as an antitumor effector molecule secreted by γδT cells.
  • HMGN2 represents a potential therapeutic target for enhancing γδT cell-mediated cancer immunotherapy.

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