Immune checkpoints: cross-disease insights and clinical dilemmas

The immune checkpoints and their inhibitors are revolutionary advances in tumour immunotherapy. Immune checkpoints, however, have a broad spectrum effect. They not only contribute to tumour immune escape, but also are involved in the regulation of the pathopathological processes of numerous inflammatory illnesses, such as sepsis, autoimmune diseases, organ transplant rejection, and viral infections, among others. Today, a considerable gap in knowledge remains regarding immune checkpoints and immune checkpoint inhibitors in non-tumour inflammatory diseases, which remains largely unaddressed. At the same time, the emergence of immune-related adverse events and resistance challenges related to the clinical use of immune checkpoint inhibitors is becoming increasingly prominent, posing a significant obstacle to their application across various diseases. To overcome such issues, this narrative review establishes a systematic framework that links immune checkpoints to various inflammatory diseases and explores the associated therapeutic and clinical challenges. These diseases pose therapeutic and clinical challenges of immune checkpoint inhibitors, which we explore. The paper not only thoroughly describes the clinical picture, pathophysiology, and interventions in immunologic adverse events but also suggests a prospective strategy to confront the existing problems with immune checkpoint inhibitors in 3 dimensions: evaluation, management, and prevention. It will attempt to present a new conceptual framework for a comprehensive understanding of the dual role of immune checkpoints (in maintaining immune homeostasis and facilitating disease progression) and to provide a solid theoretical foundation for the development of safer and more effective cross-disease immunotherapy.