George L․ Kumar, Senior Director at AstraZeneca, shared a post LinkedIn:
“Rethinking Cancer Surgery – How Preserving Lymph Nodes May Boost Immunotherapy Success.
New findings from The Peter Doherty Institute for Infection and Immunity in Melbourne, Australia published in Nature Immunology, reveal that lymph nodes are not just passive structures but critical training hubs for the immune system. They provide the specialized environment needed for stem-like T cells to survive, expand, and generate killer T cells capable of fighting cancer and chronic infections. Other immune organs, such as the spleen, lack this supportive function.
Traditionally, lymph nodes near tumors are often removed during cancer surgery to reduce the risk of spread. However, this research shows that removal may inadvertently weaken immune responses and diminish the effectiveness of immunotherapies, including checkpoint blockade and CAR-T therapies. Preserving lymph nodes could therefore improve patient outcomes by enhancing the immune system’s ability to generate effective anti-tumor responses.
The studies also identified molecular signals that regulate stem-like T cell activity, offering targets for refining immunotherapies. This may explain why some patients respond better to treatment than others – lymph node function directly shapes therapeutic success.
While the work was done in pre-clinical models, clinical collaborations are already underway (e.g., in melanoma) to validate these insights in patient samples. The ultimate goal is to integrate these discoveries into new strategies that preserve and boost lymph node function, improving the reach and effectiveness of cancer immunotherapy.”
Title: Lymph nodes fuel KLF2-dependent effector CD8+ T cell differentiation during chronic infection and checkpoint blockade.
Authors: Carlson Tsui, Leonie Heyden, Lifen Wen, Catarina Gago da Graça, Nikita Potemkin, Aleksej Frolov, Daniel Rawlinson, Lei Qin, Verena C. Wimmer, Marjan Hadian-Jazi, Darya Malko, Chun-Hsi Su, Sining Li, Kayla R. Wilson, Helena Horvatic, Sharanya K. Wijesinghe, Marcela L. Moreira, Lachlan Dryburgh, Dominik Schienstock, Lisa Rausch, Daniel T. Utzschneider, Cornelia Halin, Scott N. Mueller, Marc D. Beyer, Sammy Bedoui, Zeinab Abdullah, Jan Schröder and Axel Kallies.
Read the full article on Nature Immunology.
Title: Lymph-node-derived stem-like but not tumor-tissue-resident CD8+ T cells fuel anticancer immunity.
Authors: Sharanya K. M. Wijesinghe, Lisa Rausch, Sarah S. Gabriel, Giovanni Galletti, Marco De Luca, Lei Qin, Lifen Wen, Carlson Tsui, Kevin Man, Leonie Heyden, Teisha Mason, Lewis D. Newland, Andrew Kueh, Yang Liao, David Chisanga, Julian Swatler, Emanuele Voulaz, Giuseppe Marulli, Valentina Errico, Agnese Losurdo, Gustavo R. Rossi, Fernando Souza-Fonseca-Guimaraes, Nicholas D. Huntington, Thomas Gebhardt, Daniel T. Utzschneider, Marco J. Herold, Wei Shi, Jan Schroeder, Enrico Lugli and Axel Kallies.
Read the full article on Nature Immunology.
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