Abstract Tumors often develop an immune phenotype that closely resembles that of their host, fostering strong immune tolerance. In contrast, their metabolic profile is markedly altered to support rapid proliferation, accompanied by elevated production of reactive oxygen species (ROS). This oxidative vulnerability can be exploited by using ROS‐enhancing compounds that oxidize tumor antigens, offering a promising approach to disrupt immune tolerance and convert immunologically “cold” tumors into “hot” ones. This perspective synthesizes recent findings focused on controlled ROS generation within the tumor microenvironment to induce tumor destruction and stimulate antitumor immunity. While many ROS enhancers are based on small molecules, liposome‐based targeted delivery systems offer a versatile and efficient platform for tumor‐selective transport. Among these, peptide‐functionalized nanovehicles (liposomes and lipid nanoemulsions) stand out for their enhanced targeting precision and design flexibility, allowing tailored delivery strategies. Advances in the design of peptide‐functionalized nanovehicles reveal their potential to trigger ROS‐dependent immune activation, highlighting their promise for integrated immuno‐oncology approaches. By combining targeted delivery with oxidative modulation, these nanoplatforms provide a powerful strategy for reprogramming the tumor microenvironment and amplifying immune responses against therapy‐resistant tumors.
Călin et al. (Tue,) studied this question.