Regardless of its effect on EBV infection the chemokine
Regardless of its effect on EBV infection, the chemokine system has been found to be regulated in both nasopharyngeal cancer and Hodgkin lymphoma. As such, Hodgkin and Reed–Sternberg (HRS) cells from Hodgkin lymphoma and nasopharyngeal carcinoma cells have been shown to express CXCL8 and CCL17. Furthermore, Hodgkin lymphoma cells express high levels of CXCL9, CXCL10, CCL3, CCL5, and CCL11.
EBV-Associated Diseases Primary EBV infection often occurs in young immunocompetent children and is asymptomatic or present with nonspecific mild symptoms. However, given that EBV was originally identified in Burkitt\'s lymphoma cells and has the unique ability to transform resting B cells into highly proliferating lymphoblasts, it is not surprising that this virus is associated with a number of cancers in both immunocompromised and immunocompetent patients. In addition, EBV has been associated with autoimmune diseases involving infected B cells (see Table 3 for an overview of confirmed EBV-associated diseases).
Drug-Target Potential 7TM receptors and in particular class A receptors to which the 7TM receptors mentioned in this review belong, are highly druggable molecules. Approximately, 35% of all currently marketed drugs target class A 7TM receptors. There is no specific antiviral treatment for EBV. Current treatment strategies for EBV-associated lymphomas include B cell AUY922 (rituximab, chimeric, and monoclonal antibody against CD20), reducing immunosuppression, EBV-specific CTL infusion, and chemotherapy for PTLDs; and anti-HIV treatment for HIV-associated lymphomas.158, 159 The use of rituximab in particular has dramatically changed the overall survival of PTLD patients, but a strategy directed specifically against EBV-infected cells and genes, which play a role in the EBV-mediated pathogenesis, could likely reduce the incidence of malignancies. As such, BILF1 constitutes an obvious target as it plays a role for EBV immune evasion56, 61, 62 and has oncogenic properties both in vitro and in vivo. EBI2 has been shown to have proliferative effects ex vivo and in addition, the receptor is upregulated in PTLDs. Though the role of EBI2 in EBV life cycle is still uncertain, the aforementioned knowledge suggests that EBI2 could play a role in EBV-mediated lymphoma development and therefore EBI2 constitutes another potential drug target. Finally, the chemokine expression pattern is skewed in both Hodgkin lymphoma and nasopharyngeal carcinoma meaning that inhibition of some chemokine receptors could prove beneficial in the antiviral treatment strategy.
Introduction Natural killer (NK) cells provide protection from viral infections or cancer via their cytolytic function and interferon gamma (IFNγ) production. A major clinical goal is to harness these NK cell functions for tumor immunotherapy (Baggio et al., 2017, Johnson and Miller, 2018, Romee et al., 2016). In addition, NK cells have been implicated in the control of HIV infection either directly or by antibody-mediated lysis of infected cells (Bradley et al., 2018, Ramsuran et al., 2018). Although NK cells lack antigen-specific receptors, recent studies indicate that some responses are characterized by expansion and memory, features originally thought to be restricted to adaptive immunity. NK cells with a memory or adaptive phenotype may be particularly effective in cellular therapies targeting tumors or chronic viral infections (Cooper et al., 2018, O’Sullivan et al., 2015). In humans, circulating NK cells encompass two major subsets, known as CD56dim and CD56bright (Freud et al., 2017, Michel et al., 2016). While this distinction is based on relative expression of the cell surface molecule CD56, profound functional differences exist between human NK subsets. CD56dim cells predominate in blood, constituting ∼90% of circulating NK populations. This subset has higher cytotoxic activity than CD56bright cells. Moreover, CD56dim NK cells preferentially express the activating Fc receptor CD16, endowing them with a capacity for antibody-dependent cellular cytotoxicity (ADCC) (Nagler et al., 1989). The CD56dim NK population also encompasses two subsets, CD57− and CD57+, the latter of which has adaptive features and expands in response to human cytomegalovirus (HCMV) infection (O’Sullivan et al., 2015). The minor CD56bright population is more efficient than CD56dim NKs in the production of cytokines, including IFNγ, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-α) (Freud et al., 2017, Michel et al., 2016).