Lymph nodes found to be key to successful cancer immunotherapy

(Press-News.org) A team of researchers, led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute), explored the cellular and molecular interactions revealing how lymph nodes play a crucial role in the fight against chronic infection and cancer.

The research, published across two papers in Nature Immunology, showed that lymph nodes provide the right environment for stem-like T cells, an important type of immune cell, to survive, multiply and produce killer cells that can fight cancer or viruses. In other immune organs, such as the spleen, these cells don’t develop or proliferate as effectively, making lymph nodes essential for a strong immune response and successful immunotherapy.

The University of Melbourne’s Professor Axel Kallies, Laboratory Head at the Doherty Institute and senior author of both papers, said the findings have important implications for cancer therapy.

“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 tumour 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.”

This work may also help explain why some patients respond better to immunotherapy than others. The state and function of lymph nodes influence how well the immune system can produce cancer-fighting T cells, directly impacting the success of immunotherapy.

The University of Melbourne’s Dr Carlson Tsui, Postdoctoral Researcher at the Doherty Institute and first author of one of the papers, said the findings could help to develop new strategies to make immunotherapy more effective.

“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 tumour 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.”
 

Additional information:

Peer-reviewed papers:  Tsui C, Heyden L, et al. Lymph nodes fuel KLF2-dependent effector CD8+ T cell differentiation during chronic infection and checkpoint blockade. Nature Immunology (2025). DOI: https://doi.org/10.1038/s41590-025-02276-7   Wijesinghe SKM, Rausch L, et al. Lymph-node-derived stem-like but not tumor-tissue-resident CD8+ T cells fuel anticancer immunity. Nature Immunology (2025). DOI: https://doi.org/10.1038/s41590-025-02219-2   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.  # END #

About the Peter Doherty Institute for Infection and Immunity 

Finding solutions to prevent, treat and cure infectious diseases and understanding the complexities of the immune system requires innovative approaches and concentrated effort. This is why The University of Melbourne – a world leader in education, teaching and research excellence – and The Royal Melbourne Hospital – an internationally renowned institution providing outstanding care, treatment and medical research – have partnered to create the Peter Doherty Institute for Infection and Immunity (Doherty Institute); a centre of excellence where leading scientists and clinicians collaborate to improve human health globally. 
doherty.edu.au        /DohertyInstitute               @TheDohertyInst        #DohertyInstitute  

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