Abstract
Nuclear factor-κB (NF-κB) has been described as one of the most important molecules linking inflammation to cancer. More recently, it has become clear that NF-κB is also involved in the regulation of immune checkpoint expression. Therapeutic approaches targeting immune checkpoint molecules, enabling the immune system to initiate immune responses against tumor cells, constitute a key breakthrough in cancer treatment. This review discusses recent evidence for an association of NF-κB and immune checkpoint expression and examines the therapeutic potential of inhibitors targeting either NF-κB directly or molecules involved in NF-κB regulation in combination with immune checkpoint blockade.
Highlights
In recent years, inflammation has been more and more accepted as a hallmark of cancer and is known to play an essential role at all stages of tumorigenesis [1]
A recent study of Li and colleagues reveals that lipopolysaccharide (LPS), a pathogen-associated molecular patterns (PAMPs) recognized by Toll-like receptor (TLR)-4, increases Nuclear factor-κB (NF-κB) activation, which in turn contributes to PD-L1 upregulation in gastric cancer cells
NF-κB has been shown to regulate transcriptional and posttranslational PD-L1 expression thereby contributing to tumor immune evasion
Summary
Inflammation has been more and more accepted as a hallmark of cancer and is known to play an essential role at all stages of tumorigenesis [1]. Under physiological conditions the so called immune checkpoints, including programmed cell death protein 1 (PD-1) and T-lymphocyte-associated protein 4 (CTLA-4), are expressed among others on activated T cells The binding to their ligands PD-L1 or B7, respectively, lead to inhibition of T cell activation, maintaining immune homeostasis and preventing autoimmunity [20,21,22]. The concept of immune checkpoint inhibition aims to block PD-1/PD-L1 or CTLA4/B7 interactions by using monoclonal antibodies This leads to the activation of T cells in the TME and to the targeting of tumor cells by releasing effector cytokines and cytotoxic granules [30,31,32,33]. This review mainly focusses on the role of NF-κB associated with tumor immune checkpoint expression and examines its therapeutic potential for cancer treatment, in combination with immune checkpoint blockade therapies
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