MDSC Immune Checkpoint - c-Rel

Myeloid-derived suppressor cells (MDSCs) have garnered significant attention as they play a critical role in promoting tumor immune escape and dampening anti-tumor responses. Among the various signaling pathways and immune checkpoints associated with MDSCs, c-Rel emerges as a promising target, presenting novel opportunities for therapeutic interventions.

In this article, Creative Biolabs delves into the world of MDSC immune checkpoint c-Rel, exploring its functions, mechanisms, and potential implications in cancer therapy.

MDSCs and their Role in Tumorigenesis

MDSCs are a heterogeneous population of immature myeloid cells that accumulate in the tumor microenvironment (TME) and peripheral tissues under pathological conditions, such as cancer. These cells exhibit potent immunosuppressive properties, hindering the function of effector T cells, natural killer (NK) cells, and dendritic cells (DCs). As a result, MDSCs foster an immunosuppressive TME, providing a safe haven for tumor cells to evade immune surveillance and promote tumor growth and metastasis.

Fig. 1 Overview of MDSC accumulation, migration, and functional pathways in the TME. (Li T, et al., 2021)

A Key Player in Immune Regulation - c-Rel Transcription Factor

The NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) family of transcription factors plays a central role in regulating various immune responses. Among its members, c-Rel stands out as a unique subunit, known for its involvement in the regulation of inflammation and immunity.

• c-Rel functions as a homo- or heterodimeric transcription factor, partnering with other NF-κB subunits to regulate gene expression.
• In the context of MDSCs, c-Rel has been found to control their development, survival, and immunosuppressive activity.

Mechanisms of c-Rel in MDSC Immunosuppression

The immunosuppressive function of MDSCs is executed through various mechanisms, and c-Rel plays a pivotal role in orchestrating some of these processes.

• c-Rel has been found to regulate the production of immunosuppressive factors, such as arginase-1, inducible nitric oxide synthase (iNOS), and reactive oxygen species (ROS).
• c-Rel promotes the expression of immunosuppressive cytokines, including interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). These cytokines further contribute to the inhibition of effector immune cells and the promotion of regulatory T cell (Treg) development, creating an immunosuppressive milieu in the TME.

Targeting c-Rel in Cancer Therapy

Given its central role in MDSC-mediated immunosuppression, c-Rel emerges as an attractive target for cancer immunotherapy. By inhibiting c-Rel, it may be possible to alleviate MDSC-mediated immune suppression, restoring anti-tumor immune responses and enhancing the efficacy of existing immunotherapies.

Several approaches are being explored to target c-Rel, including

• Small molecule inhibitors
• Gene silencing techniques
• Immunotherapeutic strategies

The discovery of the MDSC immune checkpoint c-Rel has opened up new avenues in the quest to overcome immunosuppression in cancer. As research in this field progresses, the potential of c-Rel-targeted therapies to enhance existing cancer treatments becomes increasingly promising.

With continued research and innovation, Creative Biolabs help researchers to become the dream of unleashing the full potential of the immune system to combat cancer.

References

1. Li T, et al. c-Rel is a myeloid checkpoint for cancer immunotherapy. Nature Cancer, 2020, 1(5): 507-517.
2. Li T, et al. Targeting MDSC for immune-checkpoint blockade in cancer immunotherapy: current progress and new prospects. Clinical Medicine Insights: Oncology, 2021, 15: 11795549211035540.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.