New studies reveal that preserving lymph nodes during cancer surgery could improve patient responses to immunotherapy by supporting key immune cells. Led by the Peter Doherty Institute, the research emphasizes lymph nodes' crucial function in training T cells to fight tumors. The findings, published in Nature Immunology, suggest rethinking surgical practices to boost treatment effectiveness.
A team at the Peter Doherty Institute for Infection and Immunity has published two papers in Nature Immunology detailing how lymph nodes orchestrate immune responses against cancer and chronic infections. The research demonstrates that lymph nodes provide an optimal environment for stem-like T cells to survive, multiply, and produce 'killer' T cells that target tumors, unlike other organs such as the spleen.
Professor Axel Kallies, laboratory head at the Doherty Institute and senior author of both studies, explained the implications for 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,' he said. He added that removing lymph nodes—a standard procedure to prevent tumor spread—may reduce the effectiveness of therapies like checkpoint blockade and CAR T cell treatments. 'Preserving lymph nodes could strengthen immune responses and increase the effectiveness of immunotherapy.'
The studies also explore why immunotherapy outcomes vary among patients, linking it to lymph node condition and function in generating cancer-fighting T cells. Dr. Carlson Tsui, a postdoctoral researcher at the University of Melbourne and first author on one paper, noted: '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.' He advocated for therapies that preserve and enhance lymph node function to boost the body's natural defenses.
Conducted using animal models, the work was a collaboration involving institutions like University Hospital Bonn, WEHI, and ETH Zürich, funded by bodies including the National Health and Medical Research Council of Australia. Professor Shahneen Sandhu from the Peter MacCallum Cancer Centre highlighted potential clinical translation: '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.'
The papers, published in 2025, offer insights that could inform future strategies for immunotherapy and chronic infection management.