Reactive oxygen species of tumor microenvironment: Harnessing for immunogenic cell death

• Published in: Biochimica et biophysica acta. Reviews on cancer 2024-09, Vol.1879 (5), p.189154, Article 189154
• Main Authors: Malla, RamaRao, Kumari, Seema, Ganji, Swapna Priya, Srilatha, Mundla, Nellipudi, Haasita Reddy, Nagaraju, Ganji Purnachandra
• Format: Article
• Language: English
• Subjects: Animals; Cancer immunotherapy; Damage-associated molecular patterns; Humans; Immunogenic Cell Death; Immunotherapy - methods; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; Reactive Oxygen Species - metabolism; Redox homeostasis; Tumor microenvironment; Tumor Microenvironment - immunology
• ISSN: 0304-419X; 1879-2561; 1879-2561
• DOI: 10.1016/j.bbcan.2024.189154

The tumor microenvironment (TME) is a dynamic and complex system that undergoes continuous changes in its network architecture, notably affecting redox homeostasis. These alterations collectively shape a diverse ecosystem actively supporting tumor progression by influencing the cellular and molecular components of the TME. Despite the remarkable clinical advancements in cancer immunotherapy, its spectrum of clinical utility is limited by the altered TME and inadequate tumor immunogenicity. Recent studies have revealed that some conventional and targeted therapy strategies can augment the efficacy of immunotherapy even in patients with less immunogenic solid tumors. These strategies provoke immunogenic cell death (ICD) through the ROS-dependent liberation of damage-associated molecular patterns (DAMPs). These DAMPs recognize and bind with Pattern Recognition Receptors (PRRs) on immune cells, activating and maturing defense cells, ultimately leading to a robust antitumor immune response. The present review underscores the pivotal role of redox homeostasis in orchestrating the transition of TME from a cold to a hot phenotype and the ROS-ICD axis in immune response induction. Additionally, it provides up-to-date insights into strategies that leverage ROS generation to induce ICD. The comprehensive analysis aims to develop ROS-based effective cancer immunotherapies for less immunogenic tumors. Reactive oxygen species (ROS) under disrupted redox homeostasis by tumor microenvironment (TME) promotes tumor metastasis and immune evasion. [Display omitted] •Redox homeostasis acts as a predisposing factor for tumor progression.•Reactive oxygen species (ROS) promote immune evasion by weakening immunogenicity in the tumor microenvironment.•Endoplasmic reticulum stressors induce ROS-mediated immunogenic cell death.•ROS-dependent therapy strategies for immunogenic cell death enhance the antitumor immune response.