Are cancer surgeries removing the body’s secret weapon against cancer?

Published in two Nature Immunology papers, the findings show that lymph nodes create the ideal setting for stem-like T cells -- an essential type of immune cell -- to survive, multiply, and generate the "killer" T cells that target viruses and tumors. In contrast, other immune organs like the spleen do not support these processes as effectively, highlighting the lymph nodes' importance for strong immune defenses and successful immunotherapy.

According to Professor Axel Kallies, Laboratory Head at the Doherty Institute and senior author of both studies, these discoveries could reshape approaches to cancer treatment.

"Lymph nodes aren't just passive waiting rooms for immune cells, they actively train and educate T cells, and send them off to do their job," said Professor Kallies.

"Our research suggests that removing lymph nodes during cancer surgery, a common practice to prevent tumor spread, may inadvertently reduce the effectiveness of treatments, such as checkpoint blockade and CAR T cell therapies. Preserving lymph nodes could strengthen immune responses and increase the effectiveness of immunotherapy."

The research also offers insight into why some patients respond better to immunotherapy than others. The condition and function of lymph nodes appear to influence how effectively the immune system produces cancer-fighting T cells, which can directly affect treatment outcomes.

Dr. Carlson Tsui, a Postdoctoral Researcher at the University of Melbourne and first author of one of the papers, said the team's work could pave the way for more powerful and precise immune-based treatments.

"Our research identifies molecular signals that are involved in the regulation of stem-like cells and in their capacity to produce effective killer cells. These findings could guide the development and refinement of immune-based treatments for cancer and chronic infection," said Dr. Tsui.

"Furthermore, our research shows that rather than only focusing on the tumor itself, therapies should also be designed to preserve and enhance lymph node function. By targeting these critical immune hubs, we could boost the body's natural ability to fight cancer, increase the effectiveness of existing immunotherapies and help more patients respond to treatment."

Together, the two peer-reviewed papers provide a deeper understanding of how lymph nodes shape immune responses. While they are based on work with animal models, they will guide future treatment strategies for chronic infection and cancer treatment.

Professor Shahneen Sandhu, Research Lead for the Melanoma Medical Oncology Service at the Peter MacCallum Cancer Centre, commented on the clinical implications of this work.

"While this research was done in the laboratory with pre-clinical models, we're excited to study these findings in clinical samples from patients receiving immune checkpoint inhibitors, as part of an ongoing Melanoma Research Victoria collaboration with Professor Kallies," Professor Sandhu said.

"Combining clinical and preclinical studies will help us translate these discoveries from bench to bedside and back, ultimately improving outcomes for cancer patients."

Collaboration: This research was led by the Doherty Institute and conducted in collaboration with University Hospital Bonn, German Center for Neurodegenerative Diseases, WEHI, ETH Zürich, IRCCS Humanitas Research Hospital, Olivia Newton-John Cancer Research Institute and The University of Queensland.

Funding: This work was supported by the National Health and Medical Research Council of Australia (NHMRC), the Australian Research Council (ARC), Cancer Council Victoria, EMBO, the Fondazione Italiana per la Ricerca sul Cancro-Associazione Italiana per la Ricerca sul Cancro, the German Research Foundation, the Helmholtz Association, Humanitas Research Hospital, the National Collaborative Research Infrastructure Strategy (NCRIS), Phenomics Australia and the University of Melbourne.