NET-targeted therapy: effects, limitations, and potential strategies to enhance treatment efficacy.

Neutrophil extracellular traps (NETs) are complex structures released by activated neutrophils during inflammatory responses. Due to their unique potential for causing tissue damage and modulating immune responses, there is increasing interest in studying these structures as potential targets for the treatment of infectious diseases, autoimmune diseases, and cancer. However, therapeutic targeting of NETs might trigger deleterious effects that may limit treatment efficacy. NET disruption may increase the microbial load in infection; in autoimmunity, NET targeting might impair peripheral tolerance, but it might reduce adaptive immune responses in cancer. In this review, we explore the therapeutic and deleterious effects of NET-targeted therapy while shedding light on novel strategies to overcome treatment-related limitations and enhance treatment efficacy. Neutrophil extracellular traps (NETs) have the potential to cause tissue damage and modulate immune responses, generating interest in their study as potential therapeutic targets for infections, autoimmune diseases, and cancer. Pharmacological targeting of NETs ranges from drugs that prevent NETosis, such as protein arginine deiminase 4 (PAD4) inhibitors, to drugs that target NET components (i.e., DNases). Despite promising results in disease models and safety in clinical trials, therapeutic targeting of NETs can trigger deleterious effects that may limit its use; such effects include increased microbial load in infections, impaired peripheral tolerance in autoimmunity, and reduced adaptive immunity in cancer. The development of new therapeutic approaches or the administration of NET-targeting drugs with cotherapeutics might serve as strategies to overcome the limitations of existing NET-targeted therapy and potentially increase treatment efficacy. [ABSTRACT FROM AUTHOR]