Aging-related morphological change in regional lymph nodes promotes an immunosuppressive microenvironment in colorectal cancer

Background: Lymph nodes (LNs) play a central role in anti-cancer immunity, yet the influence of aging on LN morphology and function in cancer remains largely unexplored. This study aimed to elucidate the relationship between aging-related LN alterations and the tumor immune microenvironment in colorectal cancer (CRC). Methods: Mesenteric LNs from 160 CRC patients who underwent curative resection were histologically examined. LN ectasia-defined as sinusoidal dilation with loss of sinus macrophages-was quantified and correlated with clinicopathological factors, systemic inflammatory markers, and immune cell infiltration in the primary tumor (CD3, CD8, Foxp3, Iba1, CD163 by IHC). Results: LN ectasia was significantly more frequent in elderly patients (≥70 years) and in right-sided colon cancers (p=0.002). Patients with marked LN ectasia showed lower serum albumin and leukocyte counts, indicating systemic immunosenescence. Immunohistochemical analysis revealed significantly reduced infiltration of CD8⁺ cytotoxic T cells and Iba1⁺/CD163⁺ macrophages in tumors from patients with high LN ectasia, representing a “cold” immune microenvironment. However, LN ectasia was not directly associated with prognosis. Conclusions: Aging-related LN ectasia reflects functional decline of regional lymphoid structures and correlates with attenuation of local anti-tumor immune activity in CRC. LN ectasia may serve as a histopathological biomarker of LN senescence and systemic immunosuppression in elderly cancer patients.