Background: The Link Between Autoantibodies and Cancer
Scientists have long sought to understand why some people with no known risk factors develop cancer while others with significant risk never do. The answer may lie in immune proteins known as autoantibodies (auto-Abs), suggests a commentary in Cell co-authored by a team that includes Jean-Laurent Casanova, M.D., Ph.D.
The ATLAS Project: Large-Scale Exploration of Autoantibodies
Dr. Casanova, a professor at the Center for the Genetics of Host Defense and the Children's Medical Center Research Institute at UT Southwestern, leads the ATLAS team (short for Antibody Tracking for Long-term Avoidance and Surveillance). The team received a Cancer Grand Challenges grant of up to $25 million to systematically investigate the potential role of auto-Abs in promoting and preventing cancer.
“There is ample evidence that the immune system plays a significant role in cancer,” Dr. Casanova said. “Our job will be to determine if there are auto-Abs that could offer protection against cancer or drive cancer outcomes, knowledge that could have a profound impact on cancer risk assessment and treatment.”
How Do Autoantibodies Work?
Humans have billions of different antibodies, proteins randomly produced by the immune system that can bind to molecules known as antigens, including those found on bacteria, viruses, fungi, toxins, or allergens. Antibodies can neutralize these threats or mark them for destruction by immune cells. However, in people with autoimmune diseases, antibodies mistakenly bind to normal molecules in the body, causing the immune system to attack healthy cells and tissues.
Research led by Dr. Casanova and others has shown that auto-Abs can target molecules called cytokines that the immune system uses to fight infectious diseases. Scientists have discovered auto-Abs that bind to about a dozen of the 50 or so known cytokines so far. These auto-Abs have been linked to a growing range of infectious diseases and, more recently, to an inflammatory condition. As scientists have learned various ways the immune system interacts with cancer—findings that have resulted in immunotherapies such as checkpoint inhibitor drugs and CAR T-cells—a growing hypothesis has suggested that other auto-Abs could influence cancer development and growth.
Research Plan and Significance
To test this idea, the ATLAS team will catalog and study auto-Abs in a large and diverse group of volunteers. They will include people with genetic syndromes or behaviors known to promote cancer, such as heavy smokers, who have avoided the disease; aging individuals, including centenarians; identical and fraternal twins; and patients with cancers before, during, and after they receive immunotherapies. By better understanding the role of auto-Abs in cancer, researchers can develop new ways to help patients reduce their cancer risk or treat existing disease more effectively.
This work is an extension of the Casanova Lab’s longstanding focus on inborn errors of immunity, genetic disorders that affect immune system function. Over three decades, Dr. Casanova and his colleagues have uncovered more than 80 genes that, when mutated, impair the body’s ability to fight off specific infections such as influenza, West Nile virus, and COVID-19. These inborn errors of immunity to infection led his lab to discover auto-Abs against cytokines, as their consequences mimic inborn errors of immunity. The lab will continue this research alongside the ATLAS project.
Dr. Casanova earned his medical degree at Paris Descartes University and specialized in pediatrics. He completed his doctoral degree in immunology at the Pierre and Marie Curie University in Paris. He is a member of the National Academy of Sciences and the National Academy of Medicine and an Investigator of the Howard Hughes Medical Institute. His work has been recognized recently with two prestigious international awards: the 2026 Mechthild Esser Nemmers Prize in Medical Science and the 2025 Novo Nordisk Prize. This year, he also received a $5 million Governor’s University Research Initiative (GURI) grant.
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