Why Do Some Cancer Patients Have Increased Susceptibility to Common Infections? Study Sheds Light
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A multinational collaboration co-led by the Garvan Institute of Medical Research has uncovered a potential explanation for why some cancer patients receiving a type of immunotherapy called checkpoint inhibitors experience increased susceptibility to common infections.
The findings, published in the journal Immunity, provide new insights into immune responses and reveal a potential approach to preventing the common cancer therapy side effect.
"Immune checkpoint inhibitor therapies have revolutionised cancer treatment by allowing T cells to attack tumours and cancer cells more effectively. But this hasn't been without side effects -- one of which is that approximately 20% of cancer patients undergoing checkpoint inhibitor treatment experience an increased incidence of infections, a phenomenon that was previously poorly understood," says Professor Stuart Tangye, co-senior author of the study and Head of the Immunology and Immunodeficiency Lab at Garvan.
"Our findings indicate that while checkpoint inhibitors boost anti-cancer immunity, they can also handicap B cells, which are the cells of the immune system that produce antibodies to protect against common infections. This understanding is a critical first step in understanding and reducing the side effects of this cancer treatment on immunity."
The researchers focused on the molecule PD-1, which acts as a 'handbrake' on the immune system, preventing overactivation of T cells. Checkpoint inhibitor therapies work by releasing this molecular 'handbrake' to enhance the immune system's ability to fight cancer.
The study, which was conducted in collaboration with Rockefeller University in the USA and Kyoto University Graduate School of Medicine in Japan, examined the immune cells of patients with rare cases of genetic deficiency of PD-1, or its binding partner PD-L1, as well as animal models lacking PD-1 signalling. The researchers found that impaired or absent PD-1 activity can significantly reduce the diversity and quality of antibodies produced by memory B cells, i.e. the long-lived immune cells that 'remember' past infections.
Reference: https://www.garvan.org.au/news-resources/news/study-reveals-cause-of-common-cancer-immunotherapy-side-effect
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