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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

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Blocking LAIR1 signaling in immune cells inhibits tumor development

Jingjing Xie1, Xun Gui2, Mi Deng1

  • 1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, United States.

Frontiers in Immunology
|October 10, 2022
PubMed

Insights

Blocking Leukocyte Associated Immunoglobulin like Receptor 1 (LAIR1) with antagonistic antibodies enhances anti-tumor immunity. This approach reactivates T cells and impedes tumor metastasis, offering a promising new cancer immunotherapy strategy.

Area of Science:

  • Immunology
  • Cancer Biology
  • Therapeutics

Background:

  • Current immune checkpoint blockade therapies show limited efficacy in some cancers.
  • Novel molecular targets are needed to advance cancer immunology and treatment.
  • Leukocyte Associated Immunoglobulin like Receptor 1 (LAIR1) is an immune inhibitory receptor with potential therapeutic relevance.

Purpose of the Study:

  • To investigate the potential of blocking LAIR1 signaling for cancer immunotherapy.
  • To develop specific antagonistic anti-LAIR1 monoclonal antibodies.
  • To evaluate the effects of LAIR1 blockade on anti-tumor immune functions.

Main Methods:

  • Development of specific antagonistic anti-LAIR1 monoclonal antibodies.
  • In vitro assessment of antibody effects on immune cell activity (T cells, NK cells, macrophages, dendritic cells).
  • Single-cell RNA sequencing analysis of intratumoral immune cells in LAIR1 transgenic mice.
  • In vitro studies using cancer patient immune cells and in vivo studies in a humanized mouse model.

Main Results:

  • Anti-LAIR1 antibody stimulation enhanced immune cell activities in vitro.
  • LAIR1 blockade increased CD4 memory T cells and inflammatory macrophages, while decreasing pro-tumor macrophages, regulatory T cells, and plasmacytoid dendritic cells in vivo.
  • LAIR1 blockade inhibited immunosuppressive myeloid cells, reactivated T cells from cancer patients, and impeded tumor metastasis.

Conclusions:

  • Blocking LAIR1 signaling with antagonistic antibodies is a viable strategy to enhance anti-tumor immune responses.
  • This approach shows potential for reactivating anti-tumor immunity and inhibiting cancer progression.
  • LAIR1 blockade represents a promising novel strategy for developing effective cancer immunotherapies.
Keywords:
LAIR1RNAseqT cellantibodycancer immunotherapyhumanized micemyeloid cellsnatural killer cell

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