Abstract:Preface by Editor-in-chief

Abstract:Nonresolving Inflammation and Cancer: Old hypothesis, New Frontiers

Abstract:Hepatocellular carcinoma (HCC), the second cause of cancer-related death in mainland China, is mainly caused by chronic hepatitis B virus (HBV) infection. Genetic predisposition of human leukocyte antigen classⅡ contributes to the maintenance of chronic HBV infection. Nonresolving inflammation resulted from the interaction of HBV and immune system is essential for the evolution of HBV and subsequent HCC occurrence. Persistent and insufficient antiviral immunity positively selects HBV mutants. During the inflammation-promoting carcinogenesis, genome of both HBV and hepatocyte experiences an evolutionary process of "mutation- selection-adaptation". HBV mutations not only predict but also promote the occurrence of HCC. The integration of HBV genome, especially in a form of the carboxylic-terminal truncated HBV X protein, not only promotes HCC occurrence and metastasis, but also confers the resistance to antiviral treatments. Understanding the mechanisms by which HBV induces hepatocarcinogenesis will lay the foundations for decreasing and postponing HCC occurrence and metastasis in the HBV-infected subjects.

Abstract:This review provides an insight into chronic infection and inflammation-associated hepatocellular carcinoma and potential therapeutic strategies. The inflammatory immune response plays a dual role in cancer development, including hepatocellular carcinoma (HCC). Only chronic and unresolved inflammation induces HCC, which is supported by enormous studies on animal models and clinical analyses. In chronic hepatitis, direct killing of hepatocytes by liver infiltrated lymphocytes and inflammatory cytokines-induced hepatocyte apoptosis and necrosis induce persistent neo-inflammation and hepatocyte generation, which increases the risk of genetic mutation and neoplastic transformation of hepatocytes. Several inflammation-related signaling pathways are involved in hepatocarcinogenesis, including NF-κB, JAK-STAT and MAPK/ERK signaling. In addition, microRNAs (e.g. miR-122, miR124, miR-637, miR-520, and miR-195) also play a key role in HCC development. Therefore, it will be attractive to design therapeutic strategies against HCC by blocking inflammation-inducing factors, targeting pro-inflammatory cytokines and chemokines, and intervening key pathways that orchestrate neo-inflammation networks in HCC development.

Abstract:Secretion on the surface of human nasal mucosa contains many innate proteins, the key factors of which are SPLUNC1 and LPLUNC1, members of the palate, lung and nasal epithelium clone (PLUNC) family. These two proteins are highly expressed in nasopharyngeal epithelium with the relative specificity. Both of them have bacterial/permeability-increasing protein (BPI) domain which can bind to lipopolysaccharide (LPS) to inhibit or kill bacterial growth directly. They also have the immuno defense function to protect nasopharyngeal epithelium from Epstein-Barr virus (EBV) and some other pathogenic microorganism effectively. These proteins play a significant role in the process of chronic inflammation and carcinogenesis of nasopharyngeal epithelium by inhibiting the secretion of inflammatory factors, such as IL-6, through activating NF-κB and STAT3 signaling pathways. In addition, they also can suppress nasopharyngeal carcinoma (NPC) cell growth and induce cell apoptosis through MAPK and miR-141-PTEN-AKT signaling pathways when the PLUNC proteins are re-expressed in NPC cell lines. Further study about the mechanism of PLUNC protein family in pathogenesis of NPC has important significance for the prevention and treatment guidance of NPC.

Abstract:The host restriction factor Tetherin is an interferon-inducible typeⅡ membrane glycoprotein, and plays a vital role in retroviral life cycle. The unusual topology of Tetherin is important for its antiviral activity. Tetherin restricts viral replication by inhibiting enveloped virus release from the surface of infected cells. However, viruses have evolved different strategies to antagonize the antiviral action of Tetherin. The interaction between Tetherin and its antagonist is species-specific which evidenced a long term co-evolution during the fighting history between host and viruses. In this review, we focus on the current advances in our understanding of the molecular structure and antiviral activity of Tetherin, as well as the mechanism used to conteract Tetherin by its antagonists.

Abstract:Air pollution from rapid industrialization in China and cigarette smoking led to increased environmental exposure to carcinogens, such as Benzo(a)pyrene (B[a]P), nickel, arsenic, can increase the risk for lung cancer. And lung cancer has replaced liver cancer as the leading cause of death among the patients with malignant tumors in China. According to recent studies, carcinogens play major roles in the development of lung cancer and chronic inflammation mediates the carcinogenesis partly. Carcinogen exposure could activate the transcription factor such as NFAT, NF-κB, AP-1 that will enhance inflammation factor transcription and then increase their release. Moreover, this process will be promoted by creating a positive regulatory loop due to sustained activation of transcription factor from the stimulation of inflammation factor release. The chronically inflammational microenvironment induced by carcinogen will cause the initiation and development of lung cancer. The review summarizes the cellular and animal evidences linking chronic inflammation induced by environmental carcinogens to lung cancer.

Abstract:Cancer stem cells have been suggested to play key role in tumor relapse, drug-resistance and metastasis. Chronic inflammatory states have been associated with an increased risk of malignancy. Therefore, it is possible that cytokines associated with chronic inflammation, such as IL-6, IL-8 and EGF, regulate the self-renewal of cancer stem cells via NF-κB/ Stat3 pathways. In this review, we will discuss how these adaptive processes potentially become subverted to enhance the development and function of cancer stem cells.

Abstract:Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells and immature myeloid cells at different stages that are blocked from differentiating into mature myeloid cells under certain pathological conditions, such as cancer. They can exert a strong and broad-spectrum immunosuppressive function, and are regarded as one of the most important negative regulators of the immune system. It has been shown that a variety of cytokines and growth factors in the tumor environment can induce MDSCs expansion and activation through activating certain signaling pathways. Then, MDSCs use multiple mechanisms to suppress the functions of various immune cells, especially T cells, thus promoting immune tolerance to tumors. Clinical studies demonstrated that the levels of MDSCs in cancer patients was closely correlated with tumor clinical progression, and the immunotherapies targeting MDSCs are expected to become novel strategies against cancer. Here, we reviewed the recent progress about MDSCs and tumor immune tolerance, including MDSCs identification, mechanisms of MDSCs expansion and activation, mechanisms of MDSCs' immunosuppressive capability, as well as the clinical significance of MDSCs in cancer. We also discussed the remaining issues in this field that need to be elucidated.

Abstract:Within several decades, the area of inflammation and cancer has attracted great attention. During the process of tumor initiation and progression, a variety of inflammatory cytokines including interleukin-6 entangle tumor cells and the surrounding tumor microenvironment into an inflammatory net; STAT3 (signal transducers and activators of transcription 3) is the key player in the net that persistently promotes tumor development. This review begins with the composition of STAT3 signaling pathways, and discusses its role in different cell types regarding the network between tumor cells and tumor microenvironment, and its advance in translational research on targeted cancer therapy.

Abstract:Chronic inflammation, caused by persistent stimuli or other reasons, often progress to nonresolving inflammation. It contributes significantly to pathogenesis of many diseases. In recent years, the key role of chronic inflammation in the development of cancer is widely recognized and the mechanism involved has become one of the research hotspots of life science. To date, much progress has been made in this area. This review will make an overview about the link between chronic inflammation and cancer and the underlying mechanisms, and then focus on the mechanistic target of rapamycin (mTOR) signaling pathway in mediating chronic inflammation induced cancer promotion and the potential direction for future research. It is hoped to open a new window for understanding the pathways linking chronic inflammation and malignant transformation.

Abstract:Inflammasomes activation is critical for both innate and adaptive immunity through their regulation of interleukin 1?茁(IL-1?茁) and IL-18. Prolonged inflammasomes activation can lead to exaggerated expression of signaling components as well as pro-inflammatory cytokines that can damage the host, resulting in chronic inflammatory diseases and autoimmune disorders. Therefore, pathways of deactivation are important to balance the immune responses. However, recent discoveries have uncovered a plethora of pathogenic strategies to inhibit the activation of inflammasome signal pathways and the production of pro-inflammatory cytokines to evade immune responses. Elucidation of these mechanisms might be helpful to the rational design of therapy against infectious diseases and other inflammasome-dependent inflammatory processes.