Age-Related Lymph Node Remodeling and Its Impact on Antitumor Immune Surveillance and Cancer Dissemination

Lymph nodes serve as critical hubs of adaptive immunity, coordinating the activation, expansion, and trafficking of immune cells essential for effective antitumor surveillance. With advancing age, lymph nodes undergo substantial structural and functional remodeling, including stromal fibrosis, deterioration of high endothelial venule integrity, disruption of follicular architecture, lipomatous infiltration, and impaired lymphatic drainage. These alterations are accompanied by significant shifts in immune cell composition, such as reduced naïve T cell output, compromised dendritic cell migration, expansion of regulatory and exhausted T cell subsets, and the establishment of a chronic, low-grade inflammatory state commonly referred to as “inflammaging.”As cancer incidence rises markedly with age, elucidating the mechanisms by which age-related lymph node remodeling influences tumor immunity has emerged as a pressing research priority. Impaired lymph node function may attenuate the priming of tumor-specific T cells, diminish the efficacy of immunotherapeutic interventions such as immune checkpoint inhibitors, and foster a microenvironment conducive to metastatic colonization. Furthermore, aged lymph nodes may modulate the tumor microenvironment in ways that affect dissemination patterns, sentinel node involvement, and overall clinical outcomes. Despite increasing recognition of these processes, the mechanistic links between lymph node aging, tumor progression, and therapeutic response remain insufficiently characterized.This Research Topic seeks to consolidate current knowledge and present novel findings on the cellular, molecular, and structural transformations that occur in aging lymph nodes, with particular emphasis on their implications for antitumor immunity and cancer dissemination. We welcome submissions of Original Research, Review, Mini-Review, Perspective, and Methods articles addressing, but not limited to, the following themes:1. Stromal and vascular remodeling of lymph nodes during aging and its consequences for immune cell trafficking2. Age-associated alterations in dendritic cell, T cell, B cell, and NK cell function within lymphoid tissues3. The contribution of inflammaging and cellular senescence to lymph node microenvironmental changes4. Mechanisms by which aged lymph nodes influence tumor antigen presentation and T cell priming5. The impact of lymph node aging on responses to immunotherapy, including immune checkpoint inhibitors, CAR-T cell therapy, and cancer vaccines6. Sentinel lymph node biology in older patients and its implications for staging and prognosis7. Alterations in lymphatic drainage and their role in metastatic dissemination8. Preclinical models and emerging methodologies — including spatial transcriptomics, intravital imaging, and organ-on-chip platforms — for investigating aged lymphoid tissues9. Therapeutic strategies designed to restore or rejuvenate lymph node function in elderly cancer patientsBy integrating perspectives from immunology, oncology, gerontology, and lymphatic biology, this collection aims to deepen our understanding of how aging reshapes the immune landscape of lymph nodes and to identify novel avenues for improving cancer prevention, diagnosis, and treatment in older populations. Topic editors: Pinji Lei Source: https://www.frontiersin.org/research-topics/80550/age-related-lymph-node-remodeling-and-its-impact-on-antitumor-immune-surveillance-and-cancer-dissemination