Checkpoint Inhibitors: Uncovering the Trade-off Between Anti-Cancer Immunity and Increased Infection Risk

**Checkpoint inhibitors**, a groundbreaking cancer treatment, boost the immune system's T cells to effectively target and destroy cancerous tumors. However, a **study co-led by the Garvan Institute** has revealed that around 20% of cancer patients on this treatment face an increased risk of infections. This side effect was previously not well understood. The research, published in *Immunity*, examines **PD-1 and PD-L1 molecules**, which naturally act as a handbrake on the immune system to prevent overactivation of T cells. Checkpoint inhibitors work by releasing this brake, but the study found that they also reduce the diversity and quality of antibodies produced by memory B cells. This deficit results from impaired PD-1 activity, leading to a lesser ability to produce effective antibodies against common pathogens. By analyzing genetic deficiencies in PD-1 and PD-L1, the researchers discovered reduced antibody diversity and memory B cells in affected individuals, revealing the dual nature of PD-1 inhibition: enhancing anti-cancer immunity but reducing B-cell immunity. The findings suggest that monitoring B cell function and considering **immunoglobulin replacement therapy** could mitigate infection risks. The research team emphasizes the need for refined checkpoint inhibitor treatments that retain their cancer-fighting capabilities while safeguarding against infections.