Oxidative stress and antigen processing and presentation: A novel perspective for precision immunotherapy

Recently, Na Xie, an Associate Researcher at the West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Guobo Shen, an Associate Researcher at the State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, jointly published a review article entitled "Oxidative stress in antigen processing and presentation" in MedComm-Oncology. This article systematically elucidates the dynamic mechanisms of ROS regulating antigen processing and presentation, revealing the key mechanisms by which oxidative stress influences disease progression through alterations in antigen peptide generation, antigen-presentation machinery (APM), and immune cell activation. Furthermore, it innovatively proposes combined immunotherapy strategies based on redox homeostasis regulation, providing crucial theoretical guidance for promoting the basic research and clinical practice of tumor immunotherapy.

I. Oxidative Stress and Immune Interaction: A Key Hub for Disease Treatment

Antigen processing and presentation, as a central link connecting innate and adaptive immunity, are precisely regulated by ROS. Physiological concentrations of ROS can promote adaptive immune responses by regulating proteasome activity, major histocompatibility complex (MHC) molecule assembly, and co-stimulatory signal transduction. Conversely, excessive oxidative stress can lead to antigen presentation dysfunction, abnormal expression of immune checkpoints, and immune cell exhaustion. This dose-dependent effect of ROS in antigen processing and presentation exhibits significant heterogeneity in tumor immune evasion, infection immune imbalance, and the occurrence of autoimmune diseases, suggesting that the interactive network between oxidative stress and immunity is a key hub for disease treatment. A deeper understanding of this regulatory mechanism will help us to accurately grasp the dynamic balance of immune responses, providing new targets for disease treatment.

II. Targeting Redox Homeostasis: A New Strategy for Tumor Immunotherapy

Oxidative stress plays a crucial role in tumorigenesis and anti-tumor immunity, making targeting redox homeostasis an innovative direction for enhancing the efficacy of tumor immunotherapy. Through multi-level intervention approaches, such as utilizing covalent drug modification technology to target neoantigen generation, precisely regulating ROS levels to optimize antigen presentation, targeting key antioxidant/pro-oxidant pathways to reverse immunosuppression, and remodeling the lysosomal microenvironment to activate cross-presentation, it is hoped that the reprogramming of the immune microenvironment can be achieved in the future, promoting the clinical application of individualized immunotherapy. These strategies are expected to break through traditional treatment bottlenecks and open new paths for tumor immunotherapy.

III. Summary and Outlook

Redox homeostasis is essential for regulating antigen-specific immune activity. Moderate levels of ROS are crucial for the body's immunity to resist pathogens and prevent cancer. However, excessive ROS production is detrimental, impairing immune function and promoting immunosuppression. Therefore, in tumor immunotherapy, it is necessary to dynamically and precisely regulate ROS levels based on the microenvironment, focusing on combining nano-delivery, enzyme activity regulation, and immune checkpoint intervention to optimize antigen-specific immune responses. The future challenge lies in precisely controlling the spatiotemporal distribution of ROS and avoiding excessive clearance leading to insufficient immune activation, thereby promoting the clinical application of individualized immunotherapy.

See the article: 

Oxidative stress in antigen processing and presentation

https://doi.org/10.1002/mog2.70020