Long-term major histocompatibility complex class I suppression in astronauts and clinical implications

Spaceflight can disrupt astronaut immunity, including sustained downregulation of Major Histocompatibility Complex (MHC) class I genes across missions ranging from the three-day Inspiration4 flight to long-duration International Space Station stays. MHC class I downregulation is a known mechanism of immune evasion in cancer and viral infection, potentially increasing health risks during and after spaceflight. The underlying mechanisms, clinical implications and therapeutic options remain underexplored. This Perspective discusses long-term risks associated with astronaut MHC class I suppression, proposes future research directions and outlines therapeutic approaches with broader relevance to related health challenges on Earth.