Nuclear Receptors in Cancer Inflammation and Immunity

NR fine-tune physiological and pathological processes by acting as sensors of stimuli and orchestrating downstream molecular events that govern complex gene regulatory networks. The roles of dysregulated NR-mediated signaling pathways in tumorigenesis have been well documented in a variety of cancer types. Inflammatory responses in tumor microenvironments induced by oncogenic viruses or bacterial infections, autoimmune reactions, or altered gut microbiota homeostasis can be controlled by NRs. NRs can control immune reactions or influence specific immune cell subsets to regulate different cancer-related features. NR superfamily factors constitute promising therapeutic targets for cancer treatments by modulating inflammation or immunity, either locally or systematically. Members of the nuclear receptor (NR) superfamily orchestrate cellular processes that can impact on numerous cancer hallmarks. NR activity plays important roles in the tumor microenvironment by controlling inflammation and immune responses. We summarize recent insights into the diverse mechanisms by which NR activity can control tumor inflammation, the roles of different NRs in modulating tumor immunity, and the biological features of immune cells that express specific NRs in the context of cancer. NR-dependent alterations in tumor inflammation and immunity may be amenable to pharmacological manipulation and offer new clues regarding the development of novel cancer therapeutic regimens. Members of the nuclear receptor (NR) superfamily orchestrate cellular processes that can impact on numerous cancer hallmarks. NR activity plays important roles in the tumor microenvironment by controlling inflammation and immune responses. We summarize recent insights into the diverse mechanisms by which NR activity can control tumor inflammation, the roles of different NRs in modulating tumor immunity, and the biological features of immune cells that express specific NRs in the context of cancer. NR-dependent alterations in tumor inflammation and immunity may be amenable to pharmacological manipulation and offer new clues regarding the development of novel cancer therapeutic regimens. antihormone therapy used for the management of prostate cancer. cervical dysplasia; denotes the abnormal growth of cells on the surface of the cervix that could potentially progress towards cervical cancer. receptor proteins engineered to endow T cells the ability to target a specific protein of interest. The receptors are chimeric because they combine both antigen-binding and T cell-activating functions into a single receptor. a type of myeloid cells that contain cholesterol. They can form a plaque that results in atherosclerosis. a subset of innate lymphoid cells defined by expression of the transcription factor ROR-γt. They are important for regulating inflammation, immunity, and immune cell development. immune checkpoints, such as programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), are regulators of the immune system that are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. Immune checkpoint blockade therapy has been approved by the FDA for the treatment of a variety of tumor types. a CD28 superfamily inducible co-stimulatory molecule that is expressed on activated T cells. a subset of recently discovered innate immune cells derived from common lymphoid progenitor (CLP) cells belonging to the lymphoid lineage. a subset of macrophages arbitrarily categorized as 'classically activated', typically by IFN-γ or lipopolysaccharide (LPS); they produce proinflammatory cytokines, phagocytose microbes, and initiate immune responses. a subset of macrophages that are arbitrarily categorized as 'alternatively activated' and named according to the previously discovered Th2 cell-mediated anti-inflammatory response. They are activated via IL-4 and IL-13, and lead to inhibition of proinflammatory signals. clusters of mammary gland cells which form under specific conditions. surgery to remove one or both male testicles, commonly performed to treat or prevent prostate cancer from spreading. subsets include CX3CR1highLy6C− cells in mouse, and CX3CR1highCD14dimCD16+ cells in humans; they function in different disease states to scavenge damaged cells and debris from the vasculature and have been associated with wound healing, resolution of inflammation in damaged tissues, and suppression of cancer metastasis. a subgroup of immunosuppressive CD4+ T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune diseases. They generally suppress or downregulate the function and proliferation of effector T cells. a subset of interleukin 17-secreting CD8+ T cells. a lineage of CD4+ effector T cell defined by the production of IFN-γ; they promote cell-mediated immune responses and are required for host defense against pathogens and tumors. interleukin 17-secreting proinflammatory CD4+ T helper cells. a subset of T cells in a state of unresponsiveness to substances or tissues; they have the capacity to elicit an immune response in a given organism.