The landscape of cancer treatment has undergone a significant transformation with the introduction of Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit with a potential risk of developing immune-related adverse events (irAEs). Here, we reviewed and discussed the mechanisms of action of ICIs and their pivotal role in regulating the immune system to enhance the anti-tumor immune response. We scrutinized the intricate pathogenic mechanisms responsible for irAEs, arising from the evasion of self-tolerance checkpoints due to drug-induced immune modulation. We also summarized the main clinical manifestations due to irAEs categorized by organ types, detailing their incidence and associated risk factors. The occurrence of irAEs is more frequent when ICIs are combined; with neurological, cardiovascular, hematological, and rheumatic irAEs more commonly linked to PD1/PD-L1 inhibitors and cutaneous and gastrointestinal irAEs more prevalent with CTLA4 inhibitors. Due to the often-nonspecific signs and symptoms, the diagnosis of irAEs (especially for those rare ones) can be challenging. The differential with primary autoimmune disorders becomes sometimes intricate, given the clinical and pathophysiological similarities. In conclusion, considering the escalating use of ICIs, this area of research necessitates additional clinical studies and practical insights, especially the development of biomarkers for predicting immune toxicities. In addition, there is a need for heightened education for both clinicians and patients to enhance understanding and awareness.

Outer membrane vesicles (OMVs) produced by Gram-negative bacteria have emerged as a novel and flexible vaccine platform. OMVs can be decorated with foreign antigens and carry potent immunostimulatory components. Therefore, after their purification from the culture supernatant, they are ready to be formulated for vaccine use. It has been extensively demonstrated that immunization with engineered OMVs can elicit excellent antibody responses against the heterologous antigens. However, the definition of the conditions necessary to reach the optimal antibody titers still needs to be investigated. Here, we defined the protein concentrations required to induce antigen-specific antibodies, and the amount of antigen and OMVs necessary and sufficient to elicit saturating levels of antigen-specific antibodies. Since not all antigens can be expressed in OMVs, we also investigated the effectiveness of vaccines in which OMVs and purified antigens are mixed together without using any procedure for their physical association. Our data show that in most of the cases OMV–antigen mixtures are very effective in eliciting antigen-specific antibodies. This is probably due to the capacity of OMVs to “absorb” antigens, establishing sufficiently stable interactions that allow antigen–OMV co-presentation to the same antigen presenting cell. In those cases when antigen–OMV interaction is not sufficiently stable, the addition of alum to the formulation guarantees the elicitation of high titers of antigen-specific antibodies.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) predominantly affect individuals aged 55–75 years, with granulomatosis with polyangiitis (GPA) being diagnosed most often between 55 and 65 years and microscopic polyangiitis (MPA) between 65 and 75 years. Owing to the general increase in life expectancy, the average age at diagnosis increases, encompassing also those over 75 years old. Unfortunately, the exclusion of these older patients from many clinical trials has limited our understanding of the progression of these diseases in older subjects. The role of immunosenescence and aging in AAV pathogenesis and progression is underexplored, despite potential implications in the understanding of the disease, and potentially for disease management. Although AAV manifestations are largely consistent across age groups, certain features, such as renal involvement and the association with interstitial lung disease, may be more prevalent in older patients. Frailty must be a key consideration in therapeutic decision-making, especially when balancing the efficacy of immunosuppressants with potential side effects. Recent evidence supports the use of rituximab in addition to low-dose glucocorticoids for remission induction in life- or organ-threatening AAV, including in older populations. Furthermore, preliminary evidence supports that avacopan might be as efficient as glucocorticoids in these patients. The immunosuppressive treatment of AAV reduces the immune response to environmental pathogens, with rituximab worsening age-related hypogammaglobulinemia. Thus, prophylactic measures, including vaccination and Pneumocystis pneumonia prevention, as well as strategies to mitigate glucocorticoid side effects, should be implemented in AAV management.