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Gastric cancer (GC) is a complex disease with various etiologies. While Helicobacter pylori infection is still one of the leading risk factors for GC, increasing evidence suggests a link between GC and other infective agents such as Epstein Bar Virus (EBV). EBV-associated gastric cancer (EBVaGC) is now recognized as a distinct subgroup of GC, and the complex interactions between the virus and gastric mucosa may influence its development. A recent integrative analysis of the genome and proteome of GC tissues by The Cancer Genome Atlas project has identified EBVaGC as a specific subtype characterized by PIK3CA and ARID1A mutations, extensive DNA hyper-methylation, and activation of immune signaling pathways. These molecular characteristics are markers of the unique molecular profile of this subset of GC and are potential targets for therapy. This review aims to provide an overview of the current knowledge on EBVaGC. It will focus on the epidemiology, clinic-pathological features, and genetic characteristics of EBVaGC. Additionally, it will discuss recent data indicating the potential use of EBV infection as a predictive biomarker of response to chemotherapy and immune checkpoint inhibitors. The review also delves into potential therapeutic approaches for EBVaGC, including targeted therapies and adoptive immunotherapy, highlighting the promising potential of EBV as a therapeutic target.

ABSTRACTHerpes zoster (HZ) is caused by the reactivation of latent varicella zoster virus (VZV). Severe immunocompromising conditions, such as solid tumors, have been largely associated with an increased risk for HZ due to waning VZV-specific cellular immunity. With the approval of the adjuvanted glycoprotein E (gE)-based recombinant vaccine (RZV; Shingrix™, GSK) also in immunocompromised subjects, HZ is considered a vaccine-preventable disease changing perspectives in immunocompromised subjects. To date, no clinical trial has evaluated the immunogenicity in the patients with cancer undergoing immunotherapy. In this study, we describe the humoral and cell-mediated immune responses in 38 cancer patients treated with immune checkpoint inhibitors (ICIs) and receiving RZV. We used samples collected at baseline (T0), 3 weeks (T2), and 6 months (T3) after the complete RV vaccination schedule. Our data showed that a significant proportion (40,5%) of RZV recipients mounted a stronger humoral and cell-mediated immune response at 3 weeks (T2) after complete RZV vaccination schedule. Interestingly, both humoral and cell-mediated immune responses were mostly stable over 6 months (T3). Interestingly, the overall IFNγ-producing lymphocytes was mainly associated with CD4 T cell response (p = .0012). In conclusion, data from our pilot study suggest a strong and long-lasting immunogenicity of RZV in ICI-treated patients. Prospective analyses at 1 year after vaccination will be performed in order to evaluate the long-term persistence of humoral and cell-mediated response against RZV.

Germ cell tumors arise in childhood but peak at around 30 years of age. They are the most common cancers in males under the age of 35. Over 95% arise in the testes while a minority originate in extragonadal sites such as the anterior mediastinum, or mainly in childhood the pineal gland or the sacrococcygeal area. These tumors show an extraordinary sensitivity to chemotherapy (and for seminoma, also to radiation) and cure rates are relatively high even in second or subsequent relapses. Very few data are present in the literature regarding patients diagnosed after 50 years and no specific trials have been conducted in this setting. Nearly all patients reported in the literature had testicular cancers, with occasional reports of extragonadal tumors. Despite the fact that > 50 years may be considered an “elderly” population, these patients are treated with the same cisplatin containing combinations as their younger counterparts with consequent higher toxicity. In this review we will present epidemiological and clinical data from this rare population of patients with testicular cancer.