Abstract 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. Citation Format: Kosuke Kanemitsu, Rin Yamada, Daiki Yoshii, Yukio Fujiwara, Yoshiyuki Tagayasu, Teruki Sako, Kota Arima, Kohei Yamashita, Kazuto Harada, Norihisa Hanada, Yoshihiro Komohara, Masaaki Iwatsuki. Aging-related morphological change in regional lymph nodes promotes an immunosuppressive microenvironment in colorectal cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2898.
Kanemitsu et al. (Fri,) studied this question.