Oxygen and immune response

When oxygen levels drop in infected or inflamed tissue, immune cells can stop working properly—and this project aims to find out exactly how that happens. The problem is that many serious infections and chronic diseases create low-oxygen (hypoxic) conditions inside the body. Immune cells that would normally attack viruses or tumours become suppressed in these environments, allowing disease to persist. Researchers already know that a protein called HIF helps cells sense and respond to low oxygen, but they do not fully understand how HIF controls immune suppression. This project will map the specific molecular signals—including nitric oxide and a metabolite called 2-hydroxyglutarate—that macrophages and T cells use when oxygen is scarce. If successful, this work could reveal new drug targets for boosting immune responses in chronic infections and cancers. The findings might also improve CAR-T cell therapies, a type of cancer treatment where a patient’s own immune cells are engineered to attack tumours. Currently, these therapies often fail inside the low-oxygen environment of solid tumours. Understanding how 2-hydroxyglutarate affects T cell function could lead to more resilient engineered cells. This is fundamental science—it will not produce a treatment tomorrow. But similar curiosity-driven work on immune metabolism has already reshaped cancer immunotherapy in the past decade.