Autoantibodies and cancer risk draw new ATLAS research push

A new commentary in Cell argues that autoantibodies and cancer risk may be linked in ways researchers have not yet fully mapped. UT Southwestern Medical Center said the idea could help explain why some people avoid cancer despite known risks, while others develop the disease without obvious risk factors.

The commentary was co-authored by Jean-Laurent Casanova, a professor in the Center for the Genetics of Host Defense and the Children's Medical Center Research Institute at UT Southwestern. Casanova joined UT Southwestern from The Rockefeller University on July 1, bringing a lab of more than 40 scientists, trainees and students, according to the medical center.

UT Southwestern said Casanova's lab is part of ATLAS, short for Antibody Tracking for Long-term Avoidance and Surveillance. The ATLAS team is one of five groups awarded a Cancer Grand Challenges grant of up to $25 million earlier this year to study whether autoantibodies can help drive cancer, protect against it or shape treatment outcomes.

How could autoantibodies affect cancer risk?

Antibodies are immune proteins that bind to targets known as antigens, including molecules on bacteria, viruses, fungi, toxins and allergens, according to UT Southwestern. They can neutralize threats or flag them for destruction by immune cells.

Autoantibodies are antibodies that bind to the body's own normal molecules. In autoimmune diseases, UT Southwestern said, those mistaken targets can lead the immune system to attack healthy cells and tissues.

Casanova and other researchers have shown that some autoantibodies bind to cytokines, the signaling molecules the immune system uses to fight infections, according to UT Southwestern. Researchers have identified autoantibodies against about a dozen of roughly 50 known cytokines, and the Casanova Lab and others are searching for more.

Those cytokine-targeting autoantibodies have been associated with a widening set of infectious diseases and, more recently, an inflammatory condition, UT Southwestern said. The Cell commentary extends that line of thinking to cancer, where the immune system is already known to play a central role in detection, tumor control and treatment response.

What the ATLAS team plans to study

The ATLAS project is led by Paul Bastard of the Laboratory of Human Genetics of Infectious Diseases at the Imagine Institute of the Necker Hospital for Sick Children in Paris, according to UT Southwestern. The team plans to catalog and analyze autoantibodies across a large and diverse set of volunteers.

UT Southwestern said participants will include people who have cancer-promoting genetic syndromes or behaviors, such as heavy smoking, but have not developed cancer. The study will also include older adults, including centenarians; identical and fraternal twins; and cancer patients before, during and after immunotherapy.

The project will examine whether some autoantibodies are linked to cancer avoidance, cancer development, tumor growth or response to immunotherapies. Those therapies include checkpoint inhibitor drugs and chimeric antigen receptor, or CAR, T cells, both of which grew from research into how the immune system interacts with cancer.

Casanova said through UT Southwestern that identifying autoantibodies tied to cancer protection or cancer outcomes could eventually affect risk assessment and treatment. The medical center said the work builds on his lab's long-running study of inborn errors of immunity, genetic disorders that alter immune function.

Over three decades, Casanova and colleagues have identified more than 80 genes that, when mutated, weaken the body's defenses against specific infections such as influenza, West Nile virus and COVID-19, according to UT Southwestern. The lab will continue that research while taking part in the ATLAS cancer project.

This story draws on original reporting from Medical Xpress.