New Immune Checkpoint in Macrophage - SLAMF3/4

An interesting new member of the immune checkpoint family is the macrophage immune checkpoint SLAMF3/4. As a leading expert in the field of immune checkpoints, Creative Biolabs provides resources on SLAMF3/4, sharing its importance, molecular mechanism, and potential impact on therapeutic development.

Introduction to SLAMF

SLAMF consists of nine cell surface receptors involved in the regulation of immune cell activation. These molecules are expressed to varying degrees on a wide range of immune cell types.

Structure of SLAMF receptors.Fig. 1 Structure of SLAMF receptors. (Farhangnia P, et al., 2023)

SLAMF3 and SLAMF4, also known as CD229 and CD244, respectively, belong to the SLAM family. Originally identified as T cell and NK cell markers, these receptors were later found to be expressed on macrophages, revealing their role in regulating macrophage function.

Molecular Mechanisms and Functions

The SLAMF3/4 immune checkpoint orchestrates the macrophage response through complex molecular interactions. These interactions trigger downstream signaling pathways that can either enhance or inhibit macrophage activation, depending on the context.

  • SLAMF3 binding to SLAMF3 promotes macrophage phagocytosis, cytokine production and antigen presentation. This activation cascade is fine-tuned to prevent excessive immune responses.
  • SLAMF4 binds to CD48 to generate inhibitory signals that suppress macrophage activity.

The dual role of SLAMF3/4 in enhancing and inhibiting macrophage function suggests a dynamic regulatory mechanism adapted to different immune challenges.

SLAMF3/4 For Therapy Development

The discovery of SLAMF3/4 as a macrophage immune checkpoint opens up exciting avenues for therapeutic intervention. Harnessing the potential of immune checkpoints may yield new strategies for treating a range of diseases, including cancer, autoimmune diseases, and inflammatory diseases.

  • Cancer Immunotherapy
    Modulation of SLAMF3/4 enhances anti-tumor immune responses by activating macrophages to phagocytose cancer cells or present tumor antigens to T cells. Conversely, inhibition of SLAMF3/4 interactions may suppress macrophage-mediated immunosuppression in the tumor microenvironment.
  • Autoimmune Diseases
    Fine-tuning macrophage activation through SLAMF3/4 regulation has the potential to restore immune tolerance and attenuate autoimmune responses.
  • Inflammatory Diseases
    Manipulation of SLAMF3/4 may provide a novel approach to modulating inflammation and restore immune homeostasis.

The CD47/SIRPα signaling pathway is a classical pathway regulating phagocytosis in macrophages. In contrast, the SLAM family of receptors may represent a specific receptor and is expected to provide new targets for tumor immunotherapy.

Creative Biolabs recognizes the importance of this emerging immune checkpoint and its potential for therapeutic applications. As our research progresses, we will explore and capitalize on these cutting-edge discoveries. If you have a research need, please contact us.


  1. Farhangnia P, et al. SLAM-family receptors come of age as a potential molecular target in cancer immunotherapy. Frontiers in Immunology, 2023, 14: 1174138.
  2. Li D, et al. SLAMF3 and SLAMF4 are immune checkpoints that constrain macrophage phagocytosis of hematopoietic tumors. Science Immunology, 2022;7(67).

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