Bacteriophages are a unique and fascinating group of viruses, known for their highly specific ability to infect and replicate within bacterial cells. While their potential as antibacterial agents has been recognized for decades, recent research has revealed complex interactions between phages and the human immune system, offering new insights into their role in immune modulation. New evidence reveals a dynamic and intricate relationship between phages and cytokines, suggesting their ability to regulate inflammation, immune tolerance, and host–pathogen interaction. Herein, we review how phages affect the production of cytokines and the behavior of immune cells indirectly by lysis of bacterium or directly on mammalian cells. Phages have been shown to induce both pro- and anti-inflammatory responses and recently, they have been explored in personalized immunotherapy, cancer immunotherapy, and microbiome modulation, which are the focus of this review. Several challenges remain despite significant progress, including practical obstructions related to endotoxins along with host microbiome variability and regulatory issues. Nevertheless, the potential of bacteriophages to modulate immune responses makes them attractive candidates for the future of precision medicine.

Torque Teno Virus (TTV) is a highly prevalent non-pathogenic DNA virus whose plasma levels may be related to the host’s immune status. TTV gained attention about 25 years ago, but its replication is not fully understood, nor is its relationship with the host's immune system. Despite this lack of knowledge, TTV is currently being investigated as a functional biomarker of the immune system in patients with immunological damage and inflammatory diseases. Monitoring TTV viral load over time may help clinicians in making therapeutic decisions regarding immunosuppression as well as the likelihood of infectious complications. This review summarizes what we do and do not know about this enigmatic virus.

Torque Teno Virus (TTV) is a ubiquitous component of the human virome, not associated with any disease. As its load increases when the immune system is compromised, such as in kidney transplant (KT) recipients, TTV load monitoring has been proposed as a method to assess immunosuppression. In this prospective study, TTV load was measured in plasma and urine samples from 42 KT recipients, immediately before KT and in the first 150 days after it. Data obtained suggest that TTV could be a relevant marker for evaluating immune status and could be used as a guide to predict the onset of infectious complications in the follow-up of KT recipients. Since we observed no differences considering distance from transplantation, while we found a changing trend in days before viral infections, we suggest to consider changes over time in the same subjects, irrespective of time distance from transplantation.

The human virome—comprising viruses that can persist in a host, those that benefit the host, and those that remain latent—has gained increasing acceptance as a modulator of immune response toward vaccination. The factors known to influence vaccine efficacy include host genetics, age, and bacterial microbiota, while the virome is a much less considered fourth dimension. This article reviews how components of the virome such as Torque Teno Virus (TTV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and bacteriophages impact both innate and adaptive immune responses, including mechanisms of immune pre-activation, trained immunity, and molecular mimicry from both beneficial and detrimental perspectives for vaccine-induced immunization. Emphasis is given to immunocompromised populations such as transplant recipients and those with HIV, where virome composition has been shown to correlate with vaccine responsiveness. Experimental models support clinical observations on how chronic viral exposures can either enhance or inhibit vaccine efficacy. Finally, we discuss virome-aware precision vaccinology and call for the integration of the virome in the development of immunization strategies, thus improving outcomes through customization.