Type I and II interferons toward ideal vaccine and immunotherapy.

Temizoz, Burcu; Ishii, Ken J

INTRODUCTION As the body's first line of defense, innate immunity is armed with interferons (IFNs) that link innate immunity to adaptive immunity to generate long-term and protective immune responses against invading pathogens and tumors. However, regulation of IFN production is crucial because chronic IFN responses can have deleterious effects on both antitumor and antimicrobial immunity in addition to provoking autoinflammatory or autoimmune conditions. Therefore, further understanding of the mechanisms regulating IFN production is necessary for developing better vaccines and immunotherapies. AREAS COVERED In this review, we focus on the accumulated evidence on antimicrobial and antitumor activities of type I and II IFNs acquired before the COVID-19 era. We first summarize the intracellular and intercellular mechanisms regulating IFN production and signaling. Then, we discuss the mechanisms modulating the dual nature of IFNs for both antitumor and antimicrobial immune responses. Finally, we review the detrimental role of IFNs for induction of autoinflammation and autoimmunity. EXPERT OPINION Vaccines and immunotherapies activate the immune system for IFN production, which is indispensable for boosting robust antigen-specific immune responses. The current evidence suggests that the dual role of IFNs for antimicrobial and antitumor immunity is dependent not only on the timing, administration route, and dose of IFNs but also on the type of pathogen/tumor. Nevertheless, chronic IFN production may have devastating effects, such as provocation of autoinflammation that could be followed by autoimmunity. Therefore, designing vaccines or immunotherapies requires a deliberate consideration of the mechanisms modulating the dual role of IFN for each specific disease. Indeed, combinatorial therapies involving IFN-inducing adjuvants and immune-checkpoint blockers may offer therapeutic potential, especially for cancer, whereas infectious diseases require fine adjustment of timing, dose, and route of the administration for candidate IFN-based vaccines or immunotherapies.