Secretogranin 2 binds LILRB4 resulting in immunosuppression

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.