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New perspective on lymph nodes and cancer surgery
New research from the Peter Doherty Institute for Infection and Immunity suggests that lymph nodes are not merely passive waystations for immune cells but are active training hubs that shape anti-tumor and anti-viral immunity. The studies, published in Nature Immunology, show that lymph nodes provide a specialized microenvironment that supports stem-like T cells—a population that can expand, persist and give rise to potent killer T cells that attack tumors and chronic viral infections.
New research from the Doherty Institute uncovers how lymph nodes act as active training grounds for immune cells, equipping them to better fight cancer and chronic infections. Credit: Stock
Scientific background: why lymph nodes matter
Lymph nodes are small, structured organs distributed along the lymphatic system. They filter lymph fluid and coordinate adaptive immune responses by bringing together antigen-presenting cells, cytokines and T cells. Recent immunology work has identified 'stem-like' or progenitor exhausted T cells as a crucial reservoir that replenishes tumor-fighting effector T cells during prolonged immune responses. The Doherty Institute team compared how these stem-like T cells behave in lymph nodes versus other secondary lymphoid organs such as the spleen.
In preclinical models, the researchers found that the lymph node environment uniquely supports the survival and proliferation of stem-like T cells. In contrast, the spleen and other organs lacked the cellular and molecular signals needed to maintain this population, leading to weaker generation of cytotoxic (killer) T cells. That difference has direct implications for how well immunotherapies work.
Key discoveries and clinical implications
The central finding is that lymph nodes create a permissive niche where stem-like T cells persist and differentiate into effective killer cells. Because many cancer surgeries remove nearby lymph nodes to reduce the risk of metastasis, this common practice could inadvertently remove a key source of T cells needed for durable responses to immunotherapy, including checkpoint blockade and CAR T cell approaches.
What this means for immunotherapy
Preserving lymph nodes when surgically feasible could improve patient responses to immune checkpoint inhibitors and cellular therapies by maintaining the reservoir of stem-like T cells. The research also identifies molecular signals that regulate these precursor cells—information that could be used to design drugs or delivery systems that boost lymph node function or mimic its supportive cues.
Professor Axel Kallies, Laboratory Head at the Doherty Institute and senior author on the studies, summarized the implication: 'Our work reframes lymph nodes as active educators of T cells. Surgical removal of these immune hubs may reduce the body’s capacity to generate sustained anti-tumor responses.' Dr Carlson Tsui, lead author on one of the papers, added that the molecular pathways identified could guide next-generation immunotherapies aimed at strengthening these precursor populations.
From bench to bedside: translation and limitations
The studies were conducted in animal models, so clinical validation is required. The team is collaborating with clinical researchers to examine lymph node function in patients receiving checkpoint inhibitors, especially in melanoma. Professor Shahneen Sandhu of the Peter MacCallum Cancer Centre noted that integrating preclinical and clinical samples will be key to translating these findings into surgical guidelines and therapeutic strategies.
Potential clinical applications include refining sentinel lymph node biopsy practices, minimizing unnecessary node removal, and developing lymph node–targeted adjuvants or localized cytokine therapies that preserve or restore the node’s supportive niche. Other translational avenues include nanoparticle vaccines engineered to deliver stimulatory signals to lymph nodes or drug regimens that selectively enhance stem-like T cell maintenance.
Expert Insight
'This research is an important reminder that the tumor microenvironment extends beyond the tumor itself,' said Dr. Mira Patel, an immuno-oncology clinician-scientist (fictional) with experience in cellular therapies. 'Preserving or therapeutically augmenting lymph node function could be a practical way to increase the proportion of patients who benefit from checkpoint inhibitors and CAR T treatments.' Her comment underscores the potential for surgical practice and immune-based therapies to be aligned for better outcomes.
Conclusion
The Doherty Institute’s findings identify lymph nodes as critical immune training sites that sustain stem-like T cells and thereby underpin effective anti-tumor immunity. If validated in clinical studies, this work could change surgical approaches to cancer and inspire new therapies that target lymph node biology to improve responses to immunotherapy. Future research will need to confirm these mechanisms in human tissue and to design interventions that preserve or recreate the lymph node niche without compromising cancer control.
Source: scitechdaily
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