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Signal regulatory protein beta 2 is a novel positive regulator of innate anticancer immunity

Nienke Visser1, Levi Collin Nelemans1, Yuan He1

  • 1Department of Hematology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, Netherlands.

Frontiers in Immunology
|December 20, 2023
PubMed

Insights

Signal Regulatory Protein-beta 2 (SIRP-ß2) is a novel immune activator. This protein enhances innate anticancer immunity by promoting cancer cell phagocytosis and T cell activation, offering a new immunotherapy target.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Therapeutic targeting of innate anticancer immunity, such as blocking SIRP-α/CD47 interaction, shows promise in lymphoma treatment.
  • SIRP-α inhibits phagocytes, aiding cancer cell immune evasion.
  • The SIRP family includes both inhibitory and stimulatory receptors.

Purpose of the Study:

  • To investigate the role of the uncharacterized SIRP family member, SIRP-beta 2 (SIRP-ß2), in innate anticancer immunity.
  • To determine SIRP-ß2's expression patterns and functional effects on immune cells.

Main Methods:

  • Assessed SIRP-ß2 protein expression in macrophages and granulocytes.
  • Correlated endogenous SIRP-ß2 expression on granulocytes with cancer cell trogocytosis.
  • Studied the effects of ectopic SIRP-ß2 expression on macrophage functions (adhesion, differentiation, phagocytosis) and T cell activation.
  • Investigated SIRP-ß2's interaction with DAP12 and the role of lysine 202 in this interaction.

Main Results:

  • SIRP-ß2 is highly expressed in macrophages and granulocytes.
  • Endogenous SIRP-ß2 expression on granulocytes correlated with cancer cell trogocytosis.
  • Ectopic SIRP-ß2 expression enhanced macrophage adhesion, differentiation, and cancer cell phagocytosis.
  • SIRP-ß2 potentiated T cell activation via macrophage-mediated pathways.
  • SIRP-ß2 recruits DAP12 through lysine 202, which is essential for its stimulatory effects.

Conclusions:

  • SIRP-ß2 is a novel positive regulator of innate anticancer immunity.
  • SIRP-ß2 functions by recruiting DAP12 to enhance immune cell activity.
  • SIRP-ß2 represents a potential costimulatory target for developing novel innate immunotherapies.
Keywords:
SIRP-ß2antigen presentationcd47macrophagephagocytosis

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