Abstract
Cytosolic NOD-like receptors (NLRs) have been associated with human diseases including infections, cancer, and autoimmune and inflammatory disorders. These innate immune pattern recognition molecules are essential for controlling inflammatory mechanisms through induction of cytokines, chemokines, and anti-microbial genes. Upon activation, some NLRs form multi-protein complexes called inflammasomes, while others orchestrate caspase-independent nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) signaling. Moreover, NLRs and their downstream signaling components engage in an intricate crosstalk with cell death and autophagy pathways, both critical processes for cancer development. Recently, increasing evidence has extended the concept that chronic inflammation caused by abberant NLR signaling is a powerful driver of carcinogenesis, where it abets genetic mutations, tumor growth, and progression. In this review, we explore the rapidly expanding area of research regarding the expression and functions of NLRs in different types of cancers. Furthermore, we particularly focus on how maintaining tissue homeostasis and regulating tissue repair may provide a logical platform for understanding the liaisons between the NLR-driven inflammatory responses and cancer. Finally, we outline novel therapeutic approaches that target NLR signaling and speculate how these could be developed as potential pharmaceutical alternatives for cancer treatment.
Highlights
Over the past two decades, immunologists have begun to appreciate the complexity of the innate immune system, its importance as the first wave of defensive action against perceived harmful microbes or foreign particles and its functions in triggering antigen-specific responses by engaging the adaptive immune system
THERAPEUTIC STRATEGIES AND CONCLUSION It has been suggested that the strong immunomodulatory properties of NOD-like receptors (NLRs) could be exploited for mounting potent antitumorigenic responses
Mice injected with B16 melanoma cells or EL4 thymoma cells expressing flagellin from Salmonella typhimurium were shown to display dramatic resistance to tumor establishment in NLRC4 dependent manner [231]
Summary
Over the past two decades, immunologists have begun to appreciate the complexity of the innate immune system, its importance as the first wave of defensive action against perceived harmful microbes or foreign particles and its functions in triggering antigen-specific responses by engaging the adaptive immune system. FACTORS THAT INFLUENCE TUMORIGENESIS Observations by Rudolf Virchow in the nineteenth century indicated a link between inflammation and cancer, and suggested that immune and inflammatory cells are frequently present within tumors. The exact mechanism of how inflammation leads to neoplastic transformation is not fully known, it is suggested that inflammatory immune cells like macrophages and T cells are the main orchestrators of inflammation-mediated tumor progression. These cells secrete cytokines and chemokines that cause DNA damage, generate mutagenic reactive oxygen species (ROS), and supply cancer cells with growth factors [13].
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