Background/Objectives: Inflammatory bowel disease (IBD) is a chronic inflammatory condition encompassing ulcerative colitis (UC) and Crohn’s disease (CD). The role of environmental factors in the pathogenesis of IBD remains elusive. Nevertheless, evidence suggests a pivotal role of viruses, specifically Epstein–Barr virus (EBV), in the progression of IBD through mechanisms such as molecular mimicry and bystander activation. Our previous findings demonstrate EBV DNA’s significant role in exacerbating colitis symptoms and elevating the levels of the pro-autoimmune cytokine interleukin-17A (IL-17A) in an IBD mouse model via toll-like receptor 9 (TLR9). Therefore, we aimed to examine the role of EBV particles in the pathogenesis of IBD, and the potential role of TLR9 inhibition in ameliorating disease outcomes. Methods: Three days post colitis induction, EBV particles were intra-rectally injected into female C57BL/6J mice, followed by the intra-peritoneal administration of TLR9 inhibitor. Thereupon, mice were monitored daily and the disease activity index (DAI), colon lengths, and damage scores, as well as the number of cells, double-positive for IL-17A+ and IFN-γ+, and triple-positive for IL-17A+, IFN-γ+, and FOXP3+, were evaluated. Results: Our findings revealed a significant role of TLR9 inhibition in mitigating colitis features in an EBV-injected IBD mouse model compared to the control group. Conclusions: These results indicate an essential role of TLR9 in initiating immune responses against recurrent EBV reactivation events, which ultimately contributes to inflammation aggravation in IBD patients. Consequently, TLR9 could serve as a potential therapeutic target to alleviate the severe symptoms of IBD in EBV-infected individuals.

Cervical cancer remains one of the most commonly diagnosed cancers in women worldwide, with an elevated number of associated annual deaths, even though effective preventive vaccines are available. The pathophysiology of cervical cancer is well understood, with high-risk HPV as the main culprit in carcinogenesis, in addition to cell proliferation signaling alteration and tumor immune microenvironment modulation. This understanding of the disease’s molecular signatures has led to the development of several lines of treatment, especially for advanced, recurrent, persistent, or metastatic disease. For instance, Bevacizumab, a monoclonal antibody targeting angiogenesis factors, as well as Endostar, a recombinant human endostatin, have been studied and shown to improve survival in advanced disease. In contrast, anti-angiogenic Tyrosine Kinase Inhibitors had limited efficacy. Furthermore, antibody-drug conjugates such as Tisotumab Vedotin allow to deliver a highly toxic payload directly to the tumor site by binding to tissue factor, which is highly expressed in cervical tumor cells. Moreover, immunotherapy has emerged as a key treatment modality in cervical cancer by inhibiting immune checkpoint inhibitors (PD1, PD-L1, and CTLA4). In addition, therapeutic vaccines have been investigated for the treatment of localized disease by enhancing cell-mediated immunity against E6 and E7 proteins. However, more robust clinical trials are needed before these vaccines can be effectively and safely used clinically. Finally, several ongoing trials are currently evaluating new therapeutic modalities and combinations of the currently available tools in the cervical cancer treatment armamentarium.