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Related Experiment Video

Updated: Sep 14, 2025

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Secretogranin 2 binds LILRB4 resulting in immunosuppression.

Xing Yang1, Ryan Huang1, Meng Fang1

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

Nature Immunology
|July 24, 2025
PubMed
Summary
This summary is machine-generated.

Secretogranin 2 (SCG2) interacts with leukocyte immunoglobulin-like receptor B4 (LILRB4) on myeloid cells, regulating immunosuppression and tumor growth. Targeting this SCG2-LILRB4 axis may offer new therapeutic strategies for cancer.

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Area of Science:

  • Immunology
  • Endocrinology
  • Oncology

Background:

  • Immunosuppressive myeloid cells play roles in tumor development.
  • Hormonal regulation of these cells is not well understood.
  • Secretogranins are secretory proteins with unknown specific receptors.

Purpose of the Study:

  • To investigate the interaction between secretogranin 2 (SCG2) and monocytic cells.
  • To elucidate the role of the SCG2-leukocyte immunoglobulin-like receptor B4 (LILRB4) axis in tumor immunity.

Main Methods:

  • Investigated SCG2-LILRB4 interaction on monocytic cells.
  • Utilized myeloid-specific LILRB4 transgenic mice and SCG2-deficient mice.
  • Analyzed tumor growth, immune cell infiltration, and signaling pathways (STAT3 activation).

Main Results:

  • Tumor-derived SCG2 promotes tumor growth via LILRB4 in a T cell-dependent manner.
  • SCG2 deficiency reduces tumor progression and immunosuppressive monocytic cell infiltration.
  • LILRB4 blockade inhibits SCG2-induced immunosuppression and tumor growth by triggering SHP recruitment and STAT3 activation.

Conclusions:

  • SCG2 regulates monocytic immunosuppression through functional interaction with LILRB4.
  • The SCG2-LILRB4 axis is a key regulator of tumor immunity and growth.
  • This axis represents a potential therapeutic target for cancer treatment.