Aging-Related Morphological Change in Regional Lymph Nodes Promote an Immunosuppressive Microenvironment in Colorectal Cancer.

Abstract

Lymph nodes (LNs) are critical components of anti-cancer immune responses, orchestrating antigen presentation to T-cells. Aging impairs immune function, but its impact on regional LNs in cancer remains poorly understood. This study investigated age-related morphological and immunological changes in mesenteric LNs and their association with the immune microenvironment in colorectal cancer (CRC). A total of 160 patients who underwent curative resection for CRC were retrospectively analyzed. LN ectasia, defined as sinusoidal dilation accompanied by a reduction in LN sinus macrophages, was evaluated histologically. LN ectasia was significantly more frequent in elderly patients and in right-sided colon cancers. Patients with pronounced LN ectasia showed reduced serum albumin and leukocyte counts. Immunohistochemical analysis revealed that marked LN ectasia was associated with decreased infiltration of CD8+ T cells and Iba1+/CD163+ tumor-associated macrophages in the primary cancer lesion, consistent with a "cold" immune microenvironment. Although LN ectasia was not directly associated with prognosis, it reflected systemic immunosenescence and attenuated local immune activation. These findings suggest that LN ectasia serves as a histological marker of aging-related LN dysfunction, contributing to diminished anti-cancer immunity in CRC.