4-1BBL Immune Checkpoint Molecule for Drug Development

Creative Biolabs is dedicated to providing comprehensive support for your immune checkpoint research by delivering reliable theoretical knowledge on 4-1BBL.

Structure and Background of 4-1BBL

The 4-1BB molecule comprises a type I transmembrane receptor with four extracellular domains, a cytoplasmic domain, and a transmembrane helical structure. 4-1BBL is currently the only known 4-1BB cell-to-cell ligand, consisting of a short N-terminal cytoplasmic region, a transmembrane structural domain, and an extracellular TNF THD, which is typically presented in a soluble form.

4-1BB is an important tumor intervention target. (Kim, et al., 2022)Fig 1. 4-1BB is an important tumor intervention target.1

Mechanism of Action of 4-1BBL

As the binding partner of 4-1BB, effective interaction between 4-1BBL and 4-1BB leads to rapid receptor activation upon antigen stimulation. After binding, the resulting signaling pathway produces a co-stimulatory signal, which further enhances the proliferation of CD4+ and CD8+ T cells, cytokine production, and cell survival rate.

Mechanism of 4-1BB/4-1BBL. (Creative Biolabs Authorized) Fig 2. Mechanism of 4-1BB/4-1BBL.

Immunological Function and Tumor Impact of 4-1BBL

Due to its broad expression profile, the 4-1BB signaling pathway plays a crucial role in immune regulation in the human body. Both IL15 and IL-2 can promote the expression of 4-1BB on NK cells, leading to IFN-g production, T cell proliferation, and memory T cell generation. The immunological functions of the 4-1BB/4-1BBL interaction include:

  • Augmenting the immune response against pathogen infections
  • Demonstrating anti-tumor effects
  • Participating in the alleviation of various autoimmune diseases

Anti-tumor Effects of 4-1BB/4-1BBL

The anti-tumor effects of 4-1BB mAbs primarily rely on their influence on several immune cells present within the tumor microenvironment

  • Activation and proliferation of CD8+ T cells are promoted by 4-1BB mAbs, enhancing their ability to induce tumor cell lysis.
  • Interaction with CD4+ T cells stimulates the release of cytokines that activate and mature CD8+ T cells.
  • The ADCC effect of NK cells is strengthened, promoting NK cell activation, proliferation, and production of γ-interferon (IFN-γ), thereby regulating CD8+ T cell activity.
  • Depletion of DCs in vivo reduces CTL stimulation levels, weakening the effect of 4-1BB mAbs.

In summary, 4-1BBL activates diverse immune cells through the 4-1BB signal, regulating T cell activity, inducing cytokine production, preventing activation-induced cell death (AICD), and enhancing CTL activity.

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  1. Kim, et al. "4-1BB: A promising target for cancer immunotherapy." Frontiers in Oncology. 14 (2022): 968360.

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